[ { "id": "https://authors.library.caltech.edu/records/bggb8-t6b12", "eprint_status": "archive", "datestamp": "2023-11-09 23:14:31", "lastmod": "2024-01-09 22:22:45", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Barlow-Ida-L", "name": { "family": "Barlow", "given": "Ida L." }, "orcid": "0000-0003-1046-9606" }, { "id": "Mackay-Eirinn-W", "name": { "family": "Mackay", "given": "Eirinn" }, "orcid": "0000-0003-1436-2259" }, { "id": "Wheater-Emily-N-W", "name": { "family": "Wheater", "given": "Emily" }, "orcid": "0000-0002-2498-293X" }, { "id": "Goel-Aimee", "name": { "family": "Goel", "given": "Aimee" }, "orcid": "0000-0002-7381-4801" }, { "id": "Lim-Sumi", "name": { "family": "Lim", "given": "Sumi" }, "orcid": "0000-0002-1614-9753" }, { "id": "Zimmerman-Steve", "name": { "family": "Zimmerman", "given": "Steve" } }, { "id": "Woods-Ian", "name": { "family": "Woods", "given": "Ian" } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Rihel-Jason", "name": { "family": "Rihel", "given": "Jason" }, "orcid": "0000-0003-4067-2066" } ] }, "title": "The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation", "ispublished": "pub", "full_text_status": "public", "keywords": "General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology; General Medicine; General Neuroscience", "note": "
\u00a9 2023, Barlow et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
\n\nThe initial screen, discovery, and characterisation of dreammist were conducted in the lab of Alexander F Schier at Harvard University. We also would like to thank members of the Rihel lab and other UCL zebrafish groups for helpful comments on experiments and the article. We thank Shannon Shibata-Germanos for fxyd1 mutant tracking experiments, John Parnavalas for reagents, Christine Orengo for help with small peptide sequence searches, Stuart Peirson for early access to mouse transcriptomic data, and Finn Mango Bamber for the Pok\u00e9mon-card-inspired dreammist name. The work was funded by NIH grants awarded to Alexander Schier (GM085357 and HL10952505); an ERC Starting Grant (#282027) and Wellcome Trust Investigator Award (#217150/Z/19/Z) to JR; NIH grant R35 NS122172 to DAP; and a Grand Challenges PhD studentship to ILB.
\n\nIda L Barlow, Conceptualization, Resources, Data curation, Software, Formal analysis, Supervision, Validation, Investigation, Visualization, Methodology, Writing \u2013 original draft, Writing \u2013 review and editing; Eirinn Mackay, Resources, Data curation, Formal analysis; Emily Wheater, Data curation, Formal analysis, Investigation, Methodology; Aimee Goel, Formal analysis, Investigation; Sumi Lim, Data curation, Formal analysis, Validation, Investigation, Methodology, Writing \u2013 review and editing; Steve Zimmerman, Resources, Data curation, Investigation, Methodology; Ian Woods, Data curation, Formal analysis, Investigation, Methodology, Writing \u2013 review and editing; David A Prober, Conceptualization, Resources, Data curation, Formal analysis, Investigation, Methodology, Writing \u2013 original draft, Writing \u2013 review and editing; Jason Rihel, Conceptualization, Resources, Data curation, Software, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing \u2013 original draft, Project administration, Writing \u2013 review and editing
\n\nData on gene selection is included in Figure 1\u2014source data 1. Software used to analyze data are available at https://github.com/ilbarlow/Dmist (copy archived at Barlow, 2020) and https://github.com/JRihel/Sleep-Analysis/tree/Sleep-Analysis-Code (copy archived at Rihel, 2023). All fish lines are listed in Table 1 and sperm are frozen at UCL, available upon request. Primers used in this study are listed in Table 2. Tracking data used to generate the figures in this article are available at https://github.com/ilbarlow/Dmist.
The following previously published dataset was used:
Zhang Y, Chen K, Sloan SA, Scholze AR, Caneda C, Ruderisch N, Deng S, Daneman R, Barres BA, JQ Wu. 2014. An RNA-Seq transcriptome and splicing database of neurons, glia, and vascular cells of the cerebral cortex. NCBI Gene Expression Omnibus. GSE52564
\n\nThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.
\n\nRaising of genetically altered zebrafish and all experimental procedures were performed under project licence 70/7612 and PA8D4D0E5 awarded to JR under the UK Animals (Scientific Procedures) Act 1986 guidelines.
", "abstract": "Sleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a viral insertion sleep screen in larval zebrafish, we identified a novel gene, dreammist (dmist), whose loss results in behavioural hyperactivity and reduced sleep at night. The neuronally expressed dmist gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na\u207a,K\u207a-ATPase regulator, FXYD1/Phospholemman. Disruption of either fxyd1 or atp1a3a, a Na\u207a,K\u207a-ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. Since atpa1a3a and dmist mutants have elevated intracellular Na\u207a levels and non-additive effects on sleep amount at night, we propose that Dmist-dependent enhancement of Na\u207a pump function modulates neuronal excitability to maintain normal sleep behaviour.
", "date": "2023-08-07", "date_type": "published", "publication": "eLife", "volume": "12", "publisher": "eLife", "pagerange": "RP87521", "issn": "2050-084X", "official_url": "https://authors.library.caltech.edu/records/bggb8-t6b12", "funders": { "items": [ { "grant_number": "GM085357" }, { "grant_number": "HL10952505" }, { "grant_number": "282027" }, { "grant_number": "217150/Z/19/Z" }, { "grant_number": "R35 NS122172" }, {} ] }, "local_group": { "items": [ { "id": "Tianqiao-and-Chrissy-Chen-Institute-for-Neuroscience" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.7554/elife.87521", "pmcid": "PMC10406431", "primary_object": { "basename": "elife-87521-mdarchecklist1.docx", "url": "https://authors.library.caltech.edu/records/bggb8-t6b12/files/elife-87521-mdarchecklist1.docx" }, "related_objects": [ { "basename": "elife-87521.pdf", "url": "https://authors.library.caltech.edu/records/bggb8-t6b12/files/elife-87521.pdf" }, { "basename": "elife-87521-fig1-data1.xlsx", "url": "https://authors.library.caltech.edu/records/bggb8-t6b12/files/elife-87521-fig1-data1.xlsx" } ], "resource_type": "article", "pub_year": "2023", "author_list": "Barlow, Ida L.; Mackay, Eirinn; et el." }, { "id": "https://authors.library.caltech.edu/records/gpz25-v2995", "eprint_id": 119810, "eprint_status": "archive", "datestamp": "2023-08-22 18:53:19", "lastmod": "2023-12-22 23:18:46", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Pollak-Daniel-J", "name": { "family": "Pollak", "given": "Daniel J." }, "orcid": "0000-0003-3738-0361" }, { "id": "Chawla-Gautam", "name": { "family": "Chawla", "given": "Gautam" }, "orcid": "0000-0001-6478-8712" }, { "id": "Andreev-Andrey", "name": { "family": "Andreev", "given": "Andrey" }, "orcid": "0000-0002-7833-1390" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "First steps into the cloud: Using Amazon data storage and computing with Python notebooks", "ispublished": "pub", "full_text_status": "public", "keywords": "Multidisciplinary", "note": "\u00a9 2023 Pollak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. \n\nThe authors gratefully acknowledge Tom Morrell and Dr. Kristin Briney for support. Many thanks to Justin Bois for instructing course BE/Bi 103b. \n\nThe authors report the following sources of funding: NIH (R35 NS122172) awarded to DAP, NIH (T32 NS105595) awarded to DJP, and Caltech/Amazon AI4Science Cloud Credits Program grant awarded to DAP. \n\nData Availability: Supporting code and calcium imaging data is available from the Caltech Data repository (doi.org/10.22002/6ejqf-qm267). \n\nExperiments involving zebrafish were performed according to the California Institute of Technology Institutional Animal Care and Use Committee (IACUC) guidelines and by the Office of Laboratory Animal Resources at the California Institute of Technology.\n\nPublished - journal.pone.0278316.pdf
Supplemental Material - journal.pone.0278316.s001.pdf
Supplemental Material - journal.pone.0278316.s002.docx
", "abstract": "With the oncoming age of big data, biologists are encountering more use cases for cloud-based computing to streamline data processing and storage. Unfortunately, cloud platforms are difficult to learn, and there are few resources for biologists to demystify them. We have developed a guide for experimental biologists to set up cloud processing on Amazon Web Services to cheaply outsource data processing and storage. Here we provide a guide for setting up a computing environment in the cloud and showcase examples of using Python and Julia programming languages. We present example calcium imaging data in the zebrafish brain and corresponding analysis using suite2p software. Tools for budget and user management are further discussed in the attached protocol. Using this guide, researchers with limited coding experience can get started with cloud-based computing or move existing coding infrastructure into the cloud environment.", "date": "2023-02", "date_type": "published", "publication": "PLoS ONE", "volume": "18", "number": "2", "publisher": "Public Library of Science", "pagerange": "Art. No. e0278316", "id_number": "CaltechAUTHORS:20230307-205876300.2", "issn": "1932-6203", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230307-205876300.2", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R35 NS122172" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "T32 NS105595" }, { "agency": "Amazon AI4Science" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1371/journal.pone.0278316", "pmcid": "PMC9910747", "primary_object": { "basename": "journal.pone.0278316.s001.pdf", "url": "https://authors.library.caltech.edu/records/gpz25-v2995/files/journal.pone.0278316.s001.pdf" }, "related_objects": [ { "basename": "journal.pone.0278316.s002.docx", "url": "https://authors.library.caltech.edu/records/gpz25-v2995/files/journal.pone.0278316.s002.docx" }, { "basename": "journal.pone.0278316.pdf", "url": "https://authors.library.caltech.edu/records/gpz25-v2995/files/journal.pone.0278316.pdf" } ], "resource_type": "article", "pub_year": "2023", "author_list": "Pollak, Daniel J.; Chawla, Gautam; et el." }, { "id": "https://authors.library.caltech.edu/records/51vsz-7ej85", "eprint_id": 114507, "eprint_status": "archive", "datestamp": "2023-08-22 17:28:23", "lastmod": "2023-12-22 23:18:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Wagle-Mahendra", "name": { "family": "Wagle", "given": "Mahendra" }, "orcid": "0000-0003-1802-9330" }, { "id": "Zarei-Mahdi", "name": { "family": "Zarei", "given": "Mahdi" } }, { "id": "Lovett-Barron-Matthew", "name": { "family": "Lovett-Barron", "given": "Matthew" }, "orcid": "0000-0003-1425-5277" }, { "id": "Poston-Kristina-Tyler", "name": { "family": "Poston", "given": "Kristina Tyler" }, "orcid": "0000-0003-0957-8813" }, { "id": "Xu-Jin", "name": { "family": "Xu", "given": "Jin" }, "orcid": "0000-0002-5342-2341" }, { "id": "Ramey-Vince", "name": { "family": "Ramey", "given": "Vince" } }, { "id": "Pollard-Katherine-S", "name": { "family": "Pollard", "given": "Katherine S." } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Schulkin-Jay", "name": { "family": "Schulkin", "given": "Jay" }, "orcid": "0000-0002-1546-505X" }, { "id": "Deisseroth-Karl", "name": { "family": "Deisseroth", "given": "Karl" }, "orcid": "0000-0001-9440-3967" }, { "id": "Guo-Su", "name": { "family": "Guo", "given": "Su" }, "orcid": "0000-0002-7342-0108" } ] }, "title": "Brain-wide perception of the emotional valence of light is regulated by distinct hypothalamic neurons", "ispublished": "pub", "full_text_status": "public", "keywords": "Genetics; Neuroscience; Cellular and Molecular Neuroscience; Psychiatry and Mental health; Molecular Biology", "note": "\u00a9 The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. \n\nReceived 08 November 2021; Revised 25 February 2022; Accepted 06 April 2022; Published 28 April 2022. \n\nWe thank our colleagues for sharing transgenic zebrafish lines: Misha Ahrens, Herwig Baier, Josh Bonkowsky, and Adam Douglass, as well as the Zebrafish International Resource Center (ZIRC). We thank Michael Munchua and Vivian Yuan for excellent fish care, and Guo lab members for helpful discussions. This work was supported by NIH R01 GM132500 (S.G.), NIH R35 NS122172 (D.A.P.), Gladstone Institutes (K.S.P.), NIH K99MH112840 (M.L.B.). \n\nData availability: All primary data are stored on a secure server at the University of California, San Francisco and are available from the corresponding author. \n\nCode availability: Full coding implementation of all analysis tools are available at https://github.com/Mahdizarei/Brain-wide-perception-of-the-emotional-valence-of-light-is-regulated-by-distinct-hypothalamic-neuron. \n\nContributions: MW and SG designed experiments. MW and KTP performed experiments. MW, MZ, and KTP analyzed data. MLB and KD contributed the electrophysiological data. JX and DP contributed the crhb CRISPR KO line. VR and KP performed bioinformatics analysis to identify crf enhancers. JS advised on the CRF system. MW, MZ, and SG wrote the paper with input from all authors. SG supervised all aspects of the work. \n\nThe authors declare no competing interests.\n\nWagle, M., Zarei, M., Lovett-Barron, M. et al. Correction to: Brain-wide perception of the emotional valence of light is regulated by distinct hypothalamic neurons. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01647-y\n\nPublished - 41380_2022_Article_1647.pdf
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Erratum - s41380-022-01647-y.pdf
", "abstract": "Salient sensory stimuli are perceived by the brain, which guides both the timing and outcome of behaviors in a context-dependent manner. Light is such a stimulus, which is used in treating mood disorders often associated with a dysregulated hypothalamic-pituitary-adrenal stress axis. Relationships between the emotional valence of light and the hypothalamus, and how they interact to exert brain-wide impacts remain unclear. Employing larval zebrafish with analogous hypothalamic systems to mammals, we show in free-swimming animals that hypothalamic corticotropin releasing factor (CRF^(Hy)) neurons promote dark avoidance, and such role is not shared by other hypothalamic peptidergic neurons. Single-neuron projection analyses uncover processes extended by individual CRF\u1d34\u02b8 neurons to multiple targets including sensorimotor and decision-making areas. In vivo calcium imaging uncovers a complex and heterogeneous response of individual CRF\u1d34\u02b8 neurons to the light or dark stimulus, with a reduced overall sum of CRF neuronal activity in the presence of light. Brain-wide calcium imaging under alternating light/dark stimuli further identifies distinct and distributed photic response neuronal types. CRF\u1d34\u02b8 neuronal ablation increases an overall representation of light in the brain and broadly enhances the functional connectivity associated with an exploratory brain state. These findings delineate brain-wide photic perception, uncover a previously unknown role of CRF^(Hy) neurons in regulating the perception and emotional valence of light, and suggest that light therapy may alleviate mood disorders through reducing an overall sum of CRF neuronal activity.", "date": "2022-09", "date_type": "published", "publication": "Molecular Psychiatry", "volume": "27", "number": "9", "publisher": "Nature Publishing Group", "pagerange": "3777-3793", "id_number": "CaltechAUTHORS:20220428-551558200", "issn": "1359-4184", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220428-551558200", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM132500" }, { "agency": "NIH", "grant_number": "R35 NS122172" }, { "agency": "Gladstone Institutes" }, { "agency": "NIH", "grant_number": "K99MH112840" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1038/s41380-022-01567-x", "pmcid": "PMC9613822", "primary_object": { "basename": "41380_2022_1567_MOESM4_ESM.avi", "url": "https://authors.library.caltech.edu/records/51vsz-7ej85/files/41380_2022_1567_MOESM4_ESM.avi" }, "related_objects": [ { "basename": "41380_2022_1567_MOESM5_ESM.pdf", "url": "https://authors.library.caltech.edu/records/51vsz-7ej85/files/41380_2022_1567_MOESM5_ESM.pdf" }, { "basename": "41380_2022_Article_1647.pdf", "url": "https://authors.library.caltech.edu/records/51vsz-7ej85/files/41380_2022_Article_1647.pdf" }, { "basename": "s41380-022-01647-y.pdf", "url": "https://authors.library.caltech.edu/records/51vsz-7ej85/files/s41380-022-01647-y.pdf" }, { "basename": "41380_2022_1567_MOESM1_ESM.avi", "url": "https://authors.library.caltech.edu/records/51vsz-7ej85/files/41380_2022_1567_MOESM1_ESM.avi" }, { "basename": "41380_2022_1567_MOESM2_ESM.avi", "url": "https://authors.library.caltech.edu/records/51vsz-7ej85/files/41380_2022_1567_MOESM2_ESM.avi" }, { "basename": "41380_2022_1567_MOESM3_ESM.avi", "url": "https://authors.library.caltech.edu/records/51vsz-7ej85/files/41380_2022_1567_MOESM3_ESM.avi" } ], "resource_type": "article", "pub_year": "2022", "author_list": "Wagle, Mahendra; Zarei, Mahdi; et el." }, { "id": "https://authors.library.caltech.edu/records/ffrea-6fp69", "eprint_id": 114861, "eprint_status": "archive", "datestamp": "2023-08-22 15:04:16", "lastmod": "2023-12-22 23:18:50", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Tran-Steven", "name": { "family": "Tran", "given": "Steven" }, "orcid": "0000-0001-8515-8250" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Validation of Candidate Sleep Disorder Risk Genes Using Zebrafish", "ispublished": "pub", "full_text_status": "public", "keywords": "zebrafish, sleep, behavior, GWAS, CRISPR/Cas9, genetic screen; Cellular and Molecular Neuroscience; Molecular Biology", "note": "\u00a9 2022 Tran and Prober. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. \n\nReceived: 10 February 2022; Accepted: 14 March 2022; Published: 07 April 2022. \n\nThis work was funded by NIH grants R35NS122172 and R01MH121601 to DAP and a SRSF Career Development Award, Banting Postdoctoral Fellowship, and NSERC Postdoctoral Fellowship awarded to ST. \n\nAuthor Contributions. ST and DAP both contributed to the writing of this manuscript. All authors contributed to the article and approved the submitted version. \n\nThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. \n\nEdited by:\n\nRobert Gerlai, University of Toronto, Canada\nReviewed by:\n\nSubhabrata Sanyal, California Life Company (Calico), United States\nLi-En Jao, University of California, Davis, United States\n\nPublished - fnmol-15-873520.pdf
", "abstract": "Sleep disorders and chronic sleep disturbances are common and are associated with cardio-metabolic diseases and neuropsychiatric disorders. Several genetic pathways and neuronal mechanisms that regulate sleep have been described in animal models, but the genes underlying human sleep variation and sleep disorders are largely unknown. Identifying these genes is essential in order to develop effective therapies for sleep disorders and their associated comorbidities. To address this unmet health problem, genome-wide association studies (GWAS) have identified numerous genetic variants associated with human sleep traits and sleep disorders. However, in most cases, it is unclear which gene is responsible for a sleep phenotype that is associated with a genetic variant. As a result, it is necessary to experimentally validate candidate genes identified by GWAS using an animal model. Rodents are ill-suited for this endeavor due to their poor amenability to high-throughput sleep assays and the high costs associated with generating, maintaining, and testing large numbers of mutant lines. Zebrafish (Danio rerio), an alternative vertebrate model for studying sleep, allows for the rapid and cost-effective generation of mutant lines using the CRISPR/Cas9 system. Numerous zebrafish mutant lines can then be tested in parallel using high-throughput behavioral assays to identify genes whose loss affects sleep. This process identifies a gene associated with each GWAS hit that is likely responsible for the human sleep phenotype. This strategy is a powerful complement to GWAS approaches and holds great promise to identify the genetic basis for common human sleep disorders.", "date": "2022-04-07", "date_type": "published", "publication": "Frontiers in Molecular Neuroscience", "volume": "15", "publisher": "Frontiers Research Foundation", "pagerange": "Art. No. 873520", "id_number": "CaltechAUTHORS:20220520-231767000", "issn": "1662-5099", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220520-231767000", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R35NS122172" }, { "agency": "NIH", "grant_number": "R01MH121601" }, { "agency": "Sleep Research Society Foundation" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.3389/fnmol.2022.873520", "pmcid": "PMC9021570", "primary_object": { "basename": "fnmol-15-873520.pdf", "url": "https://authors.library.caltech.edu/records/ffrea-6fp69/files/fnmol-15-873520.pdf" }, "resource_type": "article", "pub_year": "2022", "author_list": "Tran, Steven and Prober, David A." }, { "id": "https://authors.library.caltech.edu/records/skrdt-ewv72", "eprint_id": 114409, "eprint_status": "archive", "datestamp": "2023-08-22 13:53:26", "lastmod": "2023-12-22 23:07:23", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lee-Daniel-A", "name": { "family": "Lee", "given": "Daniel A." }, "orcid": "0000-0001-7411-2740" }, { "id": "Oikonomou-Grigorios", "name": { "family": "Oikonomou", "given": "Grigorios" }, "orcid": "0000-0001-6797-7375" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Large-scale Analysis of Sleep in Zebrafish", "ispublished": "pub", "full_text_status": "public", "keywords": "Video tracking, Sleep, Locomotor activity, Arousal, Zebrafish, Protocol, Large-scale, High-throughput; General Medicine", "note": "\u00a9 2022 Lee et al. This article is distributed under the terms of the Creative Commons Attribution License (CC BY 4.0). \n\nPublished: Feb 05, 2022. \n\nThis protocol builds upon methods developed by Jason Rihel, David Prober and Alexander Schier (Prober et al., 2006; Rihel et al., 2010b), which were subsequently updated based on experimental and analytical advances (Lee et al., 2017, 2019 and 2020; Oikonomou et al., 2019). This work was supported by grants from the NIH (DAL: K99NS097683, F32NS084769; GO: F32NS082010; DAP: R35NS122172, R01MH121601), a NARSAD Young Investigator Grant (DAL: 25392) and a Caltech BBE Postdoctoral Fellowship (DAL). \n\nThe authors declare no conflicts of interest. \n\nEthics: Animal husbandry and experiments involving zebrafish were performed in accordance with the California Institute of Technology Institutional Animal Care and Use Committee (IACUC) guidelines and by the Office of Laboratory Animal Resources at the California Institute of Technology (animal protocol 1580).\n\nPublished - Bio-protocol4313.pdf
", "abstract": "Over the past decade, zebrafish have emerged as a powerful model for the study of vertebrate sleep and wake behaviors. Experimental evidence has demonstrated behavioral, anatomical, genetic, and pharmacological conservation of sleep between zebrafish and mammals, suggesting that discoveries in zebrafish can inform our understanding of mammalian sleep. Here, we describe a protocol for performing sleep behavioral experiments in larval zebrafish, using a high-throughput video tracking system. We explain how to set up a sleep behavioral experiment and provide guidelines on how to analyze the data. Using this protocol, a typical experiment can be completed in less than five days, and this method provides a scalable platform to perform genetic and pharmacological screens in a simple and cost-effective vertebrate model. By combining high-throughput behavioral assays with several advantageous features of zebrafish, this model system provides new opportunities to make discoveries that clarify the genetic and neurological mechanisms that regulate sleep.", "date": "2022-02-05", "date_type": "published", "publication": "Bio-protocol", "volume": "12", "number": "3", "publisher": "Bio-Protocol", "pagerange": "Art. No. e4313", "id_number": "CaltechAUTHORS:20220421-752293600", "issn": "2331-8325", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220421-752293600", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "K99NS097683" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32NS084769" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32NS082010" }, { "agency": "NIH", "grant_number": "R35NS122172" }, { "agency": "NIH", "grant_number": "R01MH121601" }, { "agency": "Brain and Behavior Research Foundation", "grant_number": "25392" }, { "agency": "Caltech Division of Biology and Biological Engineering" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.21769/bioprotoc.4313", "primary_object": { "basename": "Bio-protocol4313.pdf", "url": "https://authors.library.caltech.edu/records/skrdt-ewv72/files/Bio-protocol4313.pdf" }, "resource_type": "article", "pub_year": "2022", "author_list": "Lee, Daniel A.; Oikonomou, Grigorios; et el." }, { "id": "https://authors.library.caltech.edu/records/vmnrv-s4x05", "eprint_id": 104166, "eprint_status": "archive", "datestamp": "2023-08-22 09:22:31", "lastmod": "2023-12-22 23:18:37", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "So-Juhoon", "name": { "family": "So", "given": "Juhoon" } }, { "id": "Kim-Minwook", "name": { "family": "Kim", "given": "Minwook" } }, { "id": "Lee-Seung-Hoon", "name": { "family": "Lee", "given": "Seung\u2010Hoon" } }, { "id": "Ko-Sungjin", "name": { "family": "Ko", "given": "Sungjin" } }, { "id": "Lee-Daniel-A", "name": { "family": "Lee", "given": "Daniel A." }, "orcid": "0000-0001-7411-2740" }, { "id": "Park-Hyewon", "name": { "family": "Park", "given": "Hyewon" } }, { "id": "Azuma-Mizuki", "name": { "family": "Azuma", "given": "Mizuki" } }, { "id": "Parsons-Michael-J", "name": { "family": "Parsons", "given": "Michael J." } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David" }, "orcid": "0000-0002-7371-4675" }, { "id": "Shin-Donghun", "name": { "family": "Shin", "given": "Donghun" } } ] }, "title": "Attenuating the Epidermal Growth Factor Receptor\u2013Extracellular Signal\u2010Regulated Kinase\u2013Sex\u2010Determining Region Y\u2010Box 9 Axis Promotes Liver Progenitor Cell\u2010Mediated Liver Regeneration in Zebrafish", "ispublished": "pub", "full_text_status": "public", "keywords": "reprogramming; liver progenitor cells; oval cells; biliary epithelial cells; sox9b", "note": "\u00a9 2020 by the American Association for the Study of Liver Diseases. \n\nIssue Online: 13 April 2021; Version of Record online: 13 April 2021; Accepted manuscript online: 29 June 2020; Manuscript accepted: 03 June 2020; Manuscript revised: 02 June 2020; Manuscript received: 13 December 2019. \n\nWe thank Kirsten Sadler for Tg(fabp10a:UHRF1-GFP), Alex Nechiporuk and Ken Poss for Tg(hsp70l:dnHRAS), Sarah Child for Tg(acta2:mCherry), and Anna Huttenlocher for Tg(mpeg1:Dendra2) fish. We also thank Jinrong Peng for anti-Bhmt and anti-p53 antibodies, Junsu Kang for the I-SceI destination vector, Paul Monga, Sucha Singh, and Jackie Russell for help in H&E staining, Neil Hukriede and Michael Tsang for discussion, and George Michalopoulos, Dean Yimlamai, Andy Duncan, and Angie Kim for critical reading of the manuscript. \n\nThe work was supported by NIH grants to D.S. (DK101426, DK116993) and by the NIH/NIDDK Digestive Disease Research Core Center grant P30DK120531.\n\nAccepted Version - nihms-1620505.pdf
Supplemental Material - hep31437-sup-0001-supinfo.docx
", "abstract": "Background and Aims: The liver is a highly regenerative organ, but its regenerative capacity is compromised in severe liver injury settings. In chronic liver diseases, the number of liver progenitor cells (LPCs) correlates proportionally to disease severity, implying that their inefficient differentiation into hepatocytes exacerbates the disease. Moreover, LPCs secrete proinflammatory cytokines; thus, their prolonged presence worsens inflammation and induces fibrosis. Promoting LPC\u2010to\u2010hepatocyte differentiation in patients with advanced liver disease, for whom liver transplantation is currently the only therapeutic option, may be a feasible clinical approach because such promotion generates more functional hepatocytes and concomitantly reduces inflammation and fibrosis. \n\nApproach and Results: Here, using zebrafish models of LPC\u2010mediated liver regeneration, we present a proof of principle of such therapeutics by demonstrating a role for the epidermal growth factor receptor (EGFR) signaling pathway in differentiation of LPCs into hepatocytes. We found that suppression of EGFR signaling promoted LPC\u2010to\u2010hepatocyte differentiation through the mitogen\u2010activated ERK kinase (MEK)\u2010extracellular signal\u2010regulated kinase (ERK)\u2013sex\u2010determining region Y\u2010box 9 (SOX9) cascade. Pharmacological inhibition of EGFR or MEK/ERK promoted LPC\u2010to\u2010hepatocyte differentiation as well as genetic suppression of the EGFR\u2010ERK\u2010SOX9 axis. Moreover, Sox9b overexpression in LPCs blocked their differentiation into hepatocytes. In the zebrafish liver injury model, both hepatocytes and biliary epithelial cells contributed to LPCs. EGFR inhibition promoted the differentiation of LPCs regardless of their origin. Notably, short\u2010term treatment with EGFR inhibitors resulted in better liver recovery over the long term. \n\nConclusions: The EGFR\u2010ERK\u2010SOX9 axis suppresses LPC\u2010to\u2010hepatocyte differentiation during LPC\u2010mediated liver regeneration. We suggest EGFR inhibitors as a proregenerative therapeutic drug for patients with advanced liver disease.", "date": "2021-04", "date_type": "published", "publication": "Hepatology", "volume": "73", "number": "4", "publisher": "Wiley", "pagerange": "1494-1508", "id_number": "CaltechAUTHORS:20200630-132041344", "issn": "0270-9139", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200630-132041344", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "DK101426" }, { "agency": "NIH", "grant_number": "DK116993" }, { "agency": "NIH", "grant_number": "P30DK120531" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1002/hep.31437", "pmcid": "PMC7769917", "primary_object": { "basename": "hep31437-sup-0001-supinfo.docx", "url": "https://authors.library.caltech.edu/records/vmnrv-s4x05/files/hep31437-sup-0001-supinfo.docx" }, "related_objects": [ { "basename": "nihms-1620505.pdf", "url": "https://authors.library.caltech.edu/records/vmnrv-s4x05/files/nihms-1620505.pdf" } ], "resource_type": "article", "pub_year": "2021", "author_list": "So, Juhoon; Kim, Minwook; et el." }, { "id": "https://authors.library.caltech.edu/records/e6w2s-sht53", "eprint_id": 100443, "eprint_status": "archive", "datestamp": "2023-08-20 01:05:11", "lastmod": "2023-12-22 23:07:21", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lee-Daniel-A", "name": { "family": "Lee", "given": "Daniel A." }, "orcid": "0000-0001-7411-2740" }, { "id": "Oikonomou-Grigorios", "name": { "family": "Oikonomou", "given": "Grigorios" }, "orcid": "0000-0001-6797-7375" }, { "id": "Cammidge-Tasha", "name": { "family": "Cammidge", "given": "Tasha" } }, { "id": "Andreev-Andrey", "name": { "family": "Andreev", "given": "Andrey" }, "orcid": "0000-0002-7833-1390" }, { "id": "Hong-Young", "name": { "family": "Hong", "given": "Young" }, "orcid": "0000-0001-9548-5511" }, { "id": "Hurley-Hannah", "name": { "family": "Hurley", "given": "Hannah" } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Neuropeptide VF neurons promote sleep via the serotonergic raphe", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2020, Lee et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. \n\nReceived: 27 December 2019; Accepted: 23 November 2020; Published: 18 December 2020. \n\nWe thank members of the Prober lab for helpful discussions; Sarah Hou for experimental assistance; Uyen Pham, Chris Cook, Caressa Wong, Axel Dominguez and Alex Mack for zebrafish husbandry assistance; and Andres Collazo, Giada Spigolon, and the Beckman Institute Biological Imaging Facility for 2-photon imaging assistance. This work was supported by grants from the NIH (DAL: K99NS097683, F32NS084769; GO: F32NS082010; DAP: NS070911, NS101158), a NARSAD Young Investigator Grant (DAL: 25392) and a Caltech BBE Postdoctoral Fellowship to DAL. The authors declare no competing interests. \n\nAuthor contributions: Daniel A Lee, Conceptualization, Resources, Data curation, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing - original draft, Project administration, Writing - review and editing; Grigorios Oikonomou, Resources, Software, Methodology, Writing - review and editing; Tasha Cammidge, Young Hong, Data curation, Formal analysis, Investigation; Andrey Andreev, Resources, Data curation, Formal analysis, Validation, Investigation, Visualization, Methodology; Hannah Hurley, Formal analysis, Investigation; David A Prober, Conceptualization, Resources, Formal analysis, Supervision, Funding acquisition, Project administration,\nWriting - review and editing. \n\nEthics: Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments were performed using standard protocols (Westerfield, 1993) in accordance with the California Institute of Technology Institutional Animal Care and Use Committee guidelines and by the Office of Laboratory Animal Resources at the California Institute of Technology (animal protocol 1580). \n\nData availability: All data generated or analyzed during this study are included in the manuscript and supporting files. Details described in this paper regarding transgenic and mutant animals have been deposited at ZFIN.\n\nPublished - elife-54491-v1.pdf
Submitted - 2019.12.27.889402v1.full.pdf
Supplemental Material - elife-54491-transrepform-v1.pdf
", "abstract": "Although several sleep-regulating neuronal populations have been identified, little is known about how they interact with each other to control sleep/wake states. We previously identified neuropeptide VF (NPVF) and the hypothalamic neurons that produce it as a sleep-promoting system (Lee et al., 2017). Here we show using zebrafish that npvf-expressing neurons control sleep via the serotonergic raphe nuclei (RN), a hindbrain structure that is critical for sleep in both diurnal zebrafish and nocturnal mice. Using genetic labeling and calcium imaging, we show that npvf-expressing neurons innervate and can activate serotonergic RN neurons. We also demonstrate that chemogenetic or optogenetic stimulation of npvf-expressing neurons induces sleep in a manner that requires NPVF and serotonin in the RN. Finally, we provide genetic evidence that NPVF acts upstream of serotonin in the RN to maintain normal sleep levels. These findings reveal a novel hypothalamic-hindbrain neuronal circuit for sleep/wake control.", "date": "2020-12-18", "date_type": "published", "publication": "eLife", "volume": "9", "publisher": "eLife Sciences Publications", "pagerange": "Art. No. e54491", "id_number": "CaltechAUTHORS:20200102-084029093", "issn": "2050-084X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200102-084029093", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "K99NS097683" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32NS084769" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32NS082010" }, { "agency": "NIH", "grant_number": "NS070911" }, { "agency": "NIH", "grant_number": "NS101158" }, { "agency": "Brain and Behavior Research Foundation", "grant_number": "25392" }, { "agency": "Caltech Division of Biology and Biological Engineering" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.7554/eLife.54491", "pmcid": "PMC7748413", "primary_object": { "basename": "2019.12.27.889402v1.full.pdf", "url": "https://authors.library.caltech.edu/records/e6w2s-sht53/files/2019.12.27.889402v1.full.pdf" }, "related_objects": [ { "basename": "elife-54491-transrepform-v1.pdf", "url": "https://authors.library.caltech.edu/records/e6w2s-sht53/files/elife-54491-transrepform-v1.pdf" }, { "basename": "elife-54491-v1.pdf", "url": "https://authors.library.caltech.edu/records/e6w2s-sht53/files/elife-54491-v1.pdf" } ], "resource_type": "article", "pub_year": "2020", "author_list": "Lee, Daniel A.; Oikonomou, Grigorios; et el." }, { "id": "https://authors.library.caltech.edu/records/j4xaj-z3317", "eprint_id": 106204, "eprint_status": "archive", "datestamp": "2023-08-20 00:15:11", "lastmod": "2023-12-22 23:08:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Li-Yuwei", "name": { "family": "Li", "given": "Yuwei" }, "orcid": "0000-0001-7753-4869" }, { "id": "Gonzalez-Walter-G", "name": { "family": "Gonzalez", "given": "Walter G." }, "orcid": "0000-0003-1310-9323" }, { "id": "Andreev-Andrey", "name": { "family": "Andreev", "given": "Andrey" }, "orcid": "0000-0002-7833-1390" }, { "id": "Tang-Weiyi", "name": { "family": "Tang", "given": "Weiyi" }, "orcid": "0000-0002-1279-1001" }, { "id": "Gandhi-Shashank", "name": { "family": "Gandhi", "given": "Shashank" }, "orcid": "0000-0002-4081-4338" }, { "id": "Cunha-Alexandre", "name": { "family": "Cunha", "given": "Alexandre" }, "orcid": "0000-0002-2541-6024" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David" }, "orcid": "0000-0002-7371-4675" }, { "id": "Lois-C", "name": { "family": "Lois", "given": "Carlos" }, "orcid": "0000-0002-7305-2317" }, { "id": "Bronner-M-E", "name": { "family": "Bronner", "given": "Marianne E." }, "orcid": "0000-0003-4274-1862" } ] }, "title": "Macropinocytosis-mediated membrane recycling drives neural crest migration by delivering F-actin to the lamellipodium", "ispublished": "pub", "full_text_status": "public", "keywords": "membrane recycling | actin turnover | macropinocytosis | cell migration | neural crests", "note": "\u00a9 2020 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). \n\nContributed by Marianne E. Bronner, September 22, 2020 (sent for review June 8, 2020; reviewed by Angela Nieto and Tatjana Piotrowski) \n\nWe thank Pierre Martineau for sharing reagents and Beckman Institute Biological Imaging Facility at Caltech for sharing equipment. We thank the Beckman Institute at Caltech for financial support to the Center for Advanced Methods in Biological Image Analysis (A.C.). W.G.G. is supported by the Della Martin Foundation, the American Heart Association, and the Burroughs Wellcome Fund. S.G. is supported by the American Heart Association. This project is supported by DE024157 and R35NS111564 (to M.E.B.). \n\nData Availability. All study data are included in the article and supporting information. \n\nAuthor contributions: Y.L. and W.G.G. designed research; Y.L., W.T., and S.G. performed research; Y.L., W.G.G., and A.A. contributed new reagents/analytic tools; Y.L., W.G.G., A.A., A.C., D.P., and C.L. analyzed data; and Y.L., W.G.G., and M.E.B. wrote the paper. \n\nReviewers: A.N., Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Cient\u00edficas\u2013Universidad Miguel Hern\u00e1ndez; and T.P., Stowers Institute for Medical Research. \n\nCompeting interest statement: M.E.B. and A.N. are listed as coauthors on a 2020 Consensus Statement. They did not collaborate directly on the paper. \n\nThis article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2007229117/-/DCSupplemental.\n\nPublished - 27400.full.pdf
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", "abstract": "Individual cell migration requires front-to-back polarity manifested by lamellipodial extension. At present, it remains debated whether and how membrane motility mediates this cell morphological change. To gain insights into these processes, we perform live imaging and molecular perturbation of migrating chick neural crest cells in vivo. Our results reveal an endocytic loop formed by circular membrane flow and anterograde movement of lipid vesicles, resulting in cell polarization and locomotion. Rather than clathrin-mediated endocytosis, macropinosomes encapsulate F-actin in the cell body, forming vesicles that translocate via microtubules to deliver actin to the anterior. In addition to previously proposed local conversion of actin monomers to polymers, we demonstrate a surprising role for shuttling of F-actin across cells for lamellipodial expansion. Thus, the membrane and cytoskeleton act in concert in distinct subcellular compartments to drive forward cell migration.", "date": "2020-11-03", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "117", "number": "44", "publisher": "National Academy of Sciences", "pagerange": "27400-27411", "id_number": "CaltechAUTHORS:20201022-090820908", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201022-090820908", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Caltech Beckman Institute" }, { "agency": "Della Martin Foundation" }, { "agency": "American Heart Association" }, { "agency": "Burroughs Wellcome Fund" }, { "agency": "NIH", "grant_number": "DE024157" }, { "agency": "NIH", "grant_number": "R35NS111564" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1073/pnas.2007229117", "pmcid": "PMC7959501", "primary_object": { "basename": "pnas.2007229117.sm13.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm13.avi" }, "related_objects": [ { "basename": "27400.full.pdf", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/27400.full.pdf" }, { "basename": "pnas.2007229117.sm08.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm08.avi" }, { "basename": "pnas.2007229117.sm10.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm10.avi" }, { "basename": "pnas.2007229117.sm11.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm11.avi" }, { "basename": "pnas.2007229117.sm15.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm15.avi" }, { "basename": "pnas.2007229117.sm17.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm17.avi" }, { "basename": "pnas.2007229117.sapp.pdf", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sapp.pdf" }, { "basename": "pnas.2007229117.sm01.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm01.avi" }, { "basename": "pnas.2007229117.sm02.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm02.avi" }, { "basename": "pnas.2007229117.sm03.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm03.avi" }, { "basename": "pnas.2007229117.sm04.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm04.avi" }, { "basename": "pnas.2007229117.sm06.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm06.avi" }, { "basename": "pnas.2007229117.sm05.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm05.avi" }, { "basename": "pnas.2007229117.sm07.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm07.avi" }, { "basename": "pnas.2007229117.sm09.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm09.avi" }, { "basename": "pnas.2007229117.sm12.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm12.avi" }, { "basename": "pnas.2007229117.sm14.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm14.avi" }, { "basename": "pnas.2007229117.sm16.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm16.avi" }, { "basename": "pnas.2007229117.sm18.avi", "url": "https://authors.library.caltech.edu/records/j4xaj-z3317/files/pnas.2007229117.sm18.avi" } ], "resource_type": "article", "pub_year": "2020", "author_list": "Li, Yuwei; Gonzalez, Walter G.; et el." }, { "id": "https://authors.library.caltech.edu/records/4rkq4-a5v51", "eprint_id": 103101, "eprint_status": "archive", "datestamp": "2023-08-22 05:01:14", "lastmod": "2023-12-22 23:18:44", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Bassi-I", "name": { "family": "Bassi", "given": "Ivan" } }, { "id": "Luzzani-F", "name": { "family": "Luzzani", "given": "Francesca" } }, { "id": "Marelli-F", "name": { "family": "Marelli", "given": "Federica" } }, { "id": "Vezzoli-V", "name": { "family": "Vezzoli", "given": "Valeria" } }, { "id": "Cotellessa-L", "name": { "family": "Cotellessa", "given": "Ludovica" } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Persani-L", "name": { "family": "Persani", "given": "Luca" } }, { "id": "Gothilf-Y", "name": { "family": "Gothilf", "given": "Yoav" } }, { "id": "Bonomi-M", "name": { "family": "Bonomi", "given": "Marco" } } ] }, "title": "Prokineticin receptor 2 affects GnRH3 neuron ontogeny but not fertility in zebrafish", "ispublished": "pub", "full_text_status": "public", "keywords": "Endocrinology; Neurogenesis", "note": "\u00a9 The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. \n\nReceived 19 October 2019; Accepted 07 April 2020; Published 06 May 2020. \n\nThe study was supported by funds from IRCCS Istituto Auxologico Italiano (Ricerca Corrente funds: 05C623_2016) and funds from University of Milan \u2013 Dept. of Clinical Sciences and Community Health (Piano di sostegno alla ricerca - Linea 2 Azione B). \n\nAuthor Contributions: I.B. designed, performed and interpreted the experiments and wrote the manuscript. F.L., F.M., V.V. and L.C. performed and assisted in the experiments. D.P. provided the prokr1b^(ct814/ct814) mutant line and interpreted the experiments. M.B., Y.G., and L.P. conceived the study, supervised the publication, interpreted the experiments and wrote the manuscript. \n\nThe authors declare no competing interests.\n\nSupplemental Material - 41598_2020_64077_MOESM1_ESM.doc
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Updated - s41598-020-64077-2.pdf
Erratum - s41598-020-65551-7.pdf
", "abstract": "Prokineticin receptors (PROKR1 and PROKR2) are G protein-coupled receptors which control human central and peripheral reproductive processes. Importantly, allelic variants of PROKR2 in humans are associated with altered migration of GnRH neurons, resulting in congenital hypogonadotropic hypogonadism (CHH), a heterogeneous disease characterized by delayed/absent puberty and/or infertility. Although this association is established in humans, murine models failed to fully recapitulate the reproductive and olfactory phenotypes observed in patients harboring PROKR2 mutations. Here, taking advantage of zebrafish model we investigated the role of prokr1b (ortholog of human PROKR2) during early stages of GnRH neuronal migration. Real-Time PCR and whole mount in situ hybridization assays indicate that prokr1b spatial-temporal expression is consistent with gnrh3. Moreover, knockdown and knockout of prokr1b altered the correct development of GnRH3 fibers, a phenotype that is rescued by injection of prokr1b mRNA. These results suggest that prokr1b regulates the development of the GnRH3 system in zebrafish. Analysis of gonads development and mating experiments indicate that prokr1b is not required for fertility in zebrafish, although its loss determine changes also at the testis level. Altogether, our results support the thesis of a divergent evolution in the control of vertebrate reproduction and provide a useful in vivo model for deciphering the mechanisms underlying the effect of PROKR2 allelic variants on CHH.", "date": "2020-05-06", "date_type": "published", "publication": "Scientific Reports", "volume": "10", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 7632", "id_number": "CaltechAUTHORS:20200511-103844984", "issn": "2045-2322", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200511-103844984", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "IRCCS Istituto Auxologico Italiano", "grant_number": "05C623_2016" }, { "agency": "University of Milan" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1038/s41598-020-64077-2", "pmcid": "PMC7229164", "primary_object": { "basename": "41598_2020_64077_MOESM3_ESM.avi", "url": "https://authors.library.caltech.edu/records/4rkq4-a5v51/files/41598_2020_64077_MOESM3_ESM.avi" }, "related_objects": [ { "basename": "41598_2020_64077_MOESM4_ESM.avi", "url": "https://authors.library.caltech.edu/records/4rkq4-a5v51/files/41598_2020_64077_MOESM4_ESM.avi" }, { "basename": "41598_2020_64077_MOESM5_ESM.avi", "url": "https://authors.library.caltech.edu/records/4rkq4-a5v51/files/41598_2020_64077_MOESM5_ESM.avi" }, { "basename": "s41598-020-64077-2.pdf", "url": "https://authors.library.caltech.edu/records/4rkq4-a5v51/files/s41598-020-64077-2.pdf" }, { "basename": "s41598-020-65551-7.pdf", "url": "https://authors.library.caltech.edu/records/4rkq4-a5v51/files/s41598-020-65551-7.pdf" }, { "basename": "41598_2020_64077_MOESM1_ESM.doc", "url": "https://authors.library.caltech.edu/records/4rkq4-a5v51/files/41598_2020_64077_MOESM1_ESM.doc" }, { "basename": "41598_2020_64077_MOESM2_ESM.avi", "url": "https://authors.library.caltech.edu/records/4rkq4-a5v51/files/41598_2020_64077_MOESM2_ESM.avi" } ], "resource_type": "article", "pub_year": "2020", "author_list": "Bassi, Ivan; Luzzani, Francesca; et el." }, { "id": "https://authors.library.caltech.edu/records/h1q8y-f8a13", "eprint_id": 101909, "eprint_status": "archive", "datestamp": "2023-08-22 04:59:14", "lastmod": "2023-12-22 23:18:51", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ly-Sarah", "name": { "family": "Ly", "given": "Sarah" } }, { "id": "Lee-Daniel-A", "name": { "family": "Lee", "given": "Daniel A." }, "orcid": "0000-0001-7411-2740" }, { "id": "Strus-Ewa", "name": { "family": "Strus", "given": "Ewa" } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Naidoo-Nirinjini", "name": { "family": "Naidoo", "given": "Nirinjini" }, "orcid": "0000-0002-7463-2559" } ] }, "title": "Evolutionarily Conserved Regulation of Sleep by the Protein Translational Regulator PERK", "ispublished": "pub", "full_text_status": "public", "keywords": "sleep; Drosophila; zebrafish; protein synthesis; protein translation; PERK; proteostasis; unfolded protein response; ER stress", "note": "\u00a9 2020 Elsevier. \n\nReceived 2 August 2019, Revised 16 January 2020, Accepted 12 February 2020, Available online 12 March 2020. \n\nThe authors thank Sarah Hou and Sophie Leon for assistance in data collection. This study was funded by NIGMS (R01GM123783) to N.N. \n\nData and Code Availability: The custom MATLAB and C+ code used to analyze Drosophila sleep data has been described previously [59]. This study did not generate large datasets. Further information and requests for experimental data should be directed to and be fulfilled by the Lead Contact, Nirinjini Naidoo (naidoo@pennmedicine.upenn.edu). \n\nAuthor Contributions: S.L. and N.N. conceived the project. S.L., D.A.L., D.A.P., and N.N. were responsible for the study design and manuscript writing. S.L., D.A.L., and E.S. performed the experiments and analyzed data. D.A.P. and N.N. provided the resources for the project. \n\nThe authors declare no competing interests.\n\nAccepted Version - nihms-1576611.pdf
Supplemental Material - 1-s2.0-S0960982220302037-mmc1.pdf
", "abstract": "Sleep is a cross-species phenomenon whose evolutionary and biological function remain poorly understood. Clinical and animal studies suggest that sleep disturbance is significantly associated with disruptions in protein homeostasis\u2014or proteostasis\u2014in the brain, but the mechanism of this link has not been explored. In the cell, the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) pathway modulates proteostasis by transiently inhibiting protein synthesis in response to proteostatic stress. In this study, we examined the role of the PERK pathway in sleep regulation and provide the first evidence that PERK signaling is required to regulate normal sleep in both vertebrates and invertebrates. We show that pharmacological inhibition of PERK reduces sleep in both Drosophila and zebrafish, indicating an evolutionarily conserved requirement for PERK in sleep. Genetic knockdown of PERK activity also reduces sleep in Drosophila, whereas PERK overexpression induces sleep. Finally, we demonstrate that changes in PERK signaling directly impact wake-promoting neuropeptide expression, revealing a mechanism through which proteostatic pathways can affect sleep and wake behavior. Taken together, these results demonstrate that protein synthesis pathways like PERK could represent a general mechanism of sleep and wake regulation and provide greater insight into the relationship between sleep and proteostasis.", "date": "2020-05-04", "date_type": "published", "publication": "Current Biology", "volume": "30", "number": "9", "publisher": "Cell Press", "pagerange": "1639-1648", "id_number": "CaltechAUTHORS:20200313-142322891", "issn": "0960-9822", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200313-142322891", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01GM123783" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1016/j.cub.2020.02.030", "pmcid": "PMC8788386", "primary_object": { "basename": "1-s2.0-S0960982220302037-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/h1q8y-f8a13/files/1-s2.0-S0960982220302037-mmc1.pdf" }, "related_objects": [ { "basename": "nihms-1576611.pdf", "url": "https://authors.library.caltech.edu/records/h1q8y-f8a13/files/nihms-1576611.pdf" } ], "resource_type": "article", "pub_year": "2020", "author_list": "Ly, Sarah; Lee, Daniel A.; et el." }, { "id": "https://authors.library.caltech.edu/records/z0ajw-09t69", "eprint_id": 99872, "eprint_status": "archive", "datestamp": "2023-08-19 18:32:18", "lastmod": "2023-10-18 18:53:21", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lee-Daniel-A", "name": { "family": "Lee", "given": "Daniel A." }, "orcid": "0000-0001-7411-2740" }, { "id": "Liu-Justin", "name": { "family": "Liu", "given": "Justin" }, "orcid": "0000-0002-5338-6491" }, { "id": "Hong-Young", "name": { "family": "Hong", "given": "Young" }, "orcid": "0000-0001-9548-5511" }, { "id": "Lane-Jacqueline-M", "name": { "family": "Lane", "given": "Jacqueline M." }, "orcid": "0000-0001-6101-2855" }, { "id": "Hill-Andrew-J", "name": { "family": "Hill", "given": "Andrew J." } }, { "id": "Hou-Sarah-L", "name": { "family": "Hou", "given": "Sarah L." } }, { "id": "Wang-Heming-MED", "name": { "family": "Wang", "given": "Heming" }, "orcid": "0000-0002-1486-7495" }, { "id": "Oikonomou-Grigorios", "name": { "family": "Oikonomou", "given": "Grigorios" }, "orcid": "0000-0001-6797-7375" }, { "id": "Pham-Uyen", "name": { "family": "Pham", "given": "Uyen" } }, { "id": "Engle-Jae", "name": { "family": "Engle", "given": "Jae" } }, { "id": "Saxena-Richa", "name": { "family": "Saxena", "given": "Richa" }, "orcid": "0000-0003-2233-1065" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Evolutionarily conserved regulation of sleep by epidermal growth factor receptor signaling", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). \n\nSubmitted 21 March 2019; Accepted 17 September 2019; Published 13 November 2019. \n\nWe thank members of the Prober Lab, P. Sternberg, R. Nath, H. Wang, C. Oikonomou, and J. Bedont for feedback. We also thank H. S. Dashti, C. Singh, D. Chilin, V. Sapin, T. Cammidge, H. Hurley, and C. Cook for technical assistance. Funding: This work was supported by grants from the National Institutes of Health (NIH) (D.A.L.: K99NS097683 and F32NS084769; G.O.: F32NS082010; D.A.P.: R01NS070911 and R01NS101158; J.M.L.: T32HL007567; R.S.: R01DK107859, R01HL113338, R01DK102696, and R01DK105072) and the Mallinckrodt (to D.A.P.), Rita Allen (to D.A.P.), and Brain and Behavior Research (to D.A.P. and D.A.L.) foundations. The GTEx Project was supported by the Common Fund of the Office of the Director of the NIH and by the NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Author contributions: D.A.L., J.L., and D.A.P. conceived the project and designed the experiments. D.A.L. performed most of the experiments and analyzed the data, with assistance from J.L., Y.H., A.J.H., S.L.H., G.O., U.P., J.E. and D.A.P. J.M.L., H.W., and R.S. performed the sleep genetic association analysis. D.A.L. and D.A.P. wrote the manuscript with input from J.M.L. and R.S. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors. Custom PERL and MATLAB code used for zebrafish behavioral analysis is available upon request and posted online (35). Human sleep genetic association analysis was conducted using the U.K. Biobank Resource under application number 6818.\n\nPublished - eaax4249.full.pdf
Supplemental Material - aax4249_SM.pdf
", "abstract": "The genetic bases for most human sleep disorders and for variation in human sleep quantity and quality are largely unknown. Using the zebrafish, a diurnal vertebrate, to investigate the genetic regulation of sleep, we found that epidermal growth factor receptor (EGFR) signaling is necessary and sufficient for normal sleep levels and is required for the normal homeostatic response to sleep deprivation. We observed that EGFR signaling promotes sleep via mitogen-activated protein kinase/extracellular signal\u2013regulated kinase and RFamide neuropeptide signaling and that it regulates RFamide neuropeptide expression and neuronal activity. Consistent with these findings, analysis of a large cohort of human genetic data from participants of European ancestry revealed that common variants in genes within the EGFR signaling pathway are associated with variation in human sleep quantity and quality. These results indicate that EGFR signaling and its downstream pathways play a central and ancient role in regulating sleep and provide new therapeutic targets for sleep disorders.", "date": "2019-11", "date_type": "published", "publication": "Science Advances", "volume": "5", "number": "11", "publisher": "American Association for the Advancement of Science", "pagerange": "Art. No. eaax4249", "id_number": "CaltechAUTHORS:20191115-152248915", "issn": "2375-2548", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191115-152248915", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "K99NS097683" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32NS084769" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32NS082010" }, { "agency": "NIH", "grant_number": "R01NS070911" }, { "agency": "NIH", "grant_number": "R01NS101158" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "T32HL007567" }, { "agency": "NIH", "grant_number": "R01DK107859" }, { "agency": "NIH", "grant_number": "R01HL113338" }, { "agency": "NIH", "grant_number": "R01DK102696" }, { "agency": "NIH", "grant_number": "R01DK105072" }, { "agency": "Mallinckrodt Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Brain and Behavior Research Foundation" }, { "agency": "National Cancer Institute" }, { "agency": "National Human Genome Research Institute" }, { "agency": "National Heart, Lung, and Blood Institute" }, { "agency": "National Institute on Drug Abuse" }, { "agency": "National Institute of Mental Health (NIMH)" }, { "agency": "National Institute of Neurological Disorders and Stroke (NINDS)" } ] }, "doi": "10.1126/sciadv.aax4249", "pmcid": "PMC6853770", "primary_object": { "basename": "aax4249_SM.pdf", "url": "https://authors.library.caltech.edu/records/z0ajw-09t69/files/aax4249_SM.pdf" }, "related_objects": [ { "basename": "eaax4249.full.pdf", "url": "https://authors.library.caltech.edu/records/z0ajw-09t69/files/eaax4249.full.pdf" } ], "resource_type": "article", "pub_year": "2019", "author_list": "Lee, Daniel A.; Liu, Justin; et el." }, { "id": "https://authors.library.caltech.edu/records/18xb6-7gx83", "eprint_id": 98918, "eprint_status": "archive", "datestamp": "2023-08-19 18:04:59", "lastmod": "2023-10-18 17:43:59", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ruzzo-E-K", "name": { "family": "Ruzzo", "given": "Elizabeth" } }, { "id": "P\u00e9rez-Cano-L", "name": { "family": "P\u00e9rez-Cano", "given": "Laura" } }, { "id": "Jung-Jae-Yoon", "name": { "family": "Jung", "given": "Jae-Yoon" } }, { "id": "Wang-Lee-kai", "name": { "family": "Wang", "given": "Lee-kai" } }, { "id": "Kashef-Haghighi-D", "name": { "family": "Kashef-Haghighi", "given": "Dorna" } }, { "id": "Hartl-C", "name": { "family": "Hartl", "given": "Chris" } }, { "id": "Lowe-J-K", "name": { "family": "Lowe", "given": "Jennifer" } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David" }, "orcid": "0000-0002-7371-4675" }, { "id": "Wall-D-P", "name": { "family": "Wall", "given": "Dennis" } }, { "id": "Geschwind-D-H", "name": { "family": "Geschwind", "given": "Daniel" }, "orcid": "0000-0003-2896-3450" } ] }, "title": "Inherited and De Novo Genetic Risk for Autism Impacts Shared Biological Networks", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 Published by Elsevier. \n\nAvailable online 27 September 2019.", "abstract": "[no abstract]", "date": "2019-10", "date_type": "published", "publication": "European Neuropsychopharmacology", "volume": "29", "number": "S5", "publisher": "Elsevier", "pagerange": "S35-S36", "id_number": "CaltechAUTHORS:20190930-110456251", "issn": "0924-977X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190930-110456251", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1016/j.euroneuro.2019.07.072", "resource_type": "article", "pub_year": "2019", "author_list": "Ruzzo, Elizabeth; P\u00e9rez-Cano, Laura; et el." }, { "id": "https://authors.library.caltech.edu/records/68z2a-3w124", "eprint_id": 98268, "eprint_status": "archive", "datestamp": "2023-08-19 17:28:38", "lastmod": "2023-10-18 17:12:28", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Mosser-E-A", "name": { "family": "Mosser", "given": "Eric A." } }, { "id": "Chiu-Cindy-N", "name": { "family": "Chiu", "given": "Cindy N." } }, { "id": "Tamai-T-Katherine", "name": { "family": "Tamai", "given": "T. Katherine" } }, { "id": "Hirota-Tsuyoshi", "name": { "family": "Hirota", "given": "Tsuyoshi" }, "orcid": "0000-0003-4876-3608" }, { "id": "Li-Suna", "name": { "family": "Li", "given": "Suna" }, "orcid": "0000-0002-3431-0061" }, { "id": "Hui-May", "name": { "family": "Hui", "given": "May" } }, { "id": "Wang-Amy", "name": { "family": "Wang", "given": "Amy" } }, { "id": "Singh-C", "name": { "family": "Singh", "given": "Chanpreet" }, "orcid": "0000-0002-2697-3033" }, { "id": "Giovanni-A", "name": { "family": "Giovanni", "given": "Andrew" } }, { "id": "Kaye-S-A", "name": { "family": "Kaye", "given": "Steve A." } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Identification of pathways that regulate circadian rhythms using a larval zebrafish small molecule screen", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. \n\nReceived 21 March 2018; Accepted 31 July 2019; Published 27 August 2019. \n\nData Availability: The datasets generated and analyzed in the current study are available from the corresponding author on reasonable request. \n\nWe thank Daisy Chilin, Viveca Sapin, Ayato Sato and Natsuko Ono for technical assistance, and William Hurst and Sanofi-Aventis for providing reagents. This work was supported by grants from the NIH (NS070911, NS101158, NS095824, NS101665) and Sanofi-Aventis to D.A.P., and the JSPS (15H05590) to T.H. \n\nAuthor Contributions: E.A.M. and D.A.P. designed research. E.A.M., S.L., M.H. and A.W. performed the screen. E.A.M. and C.S. performed additional experiments. E.A.M. and C.N.C. analyzed data. T.K.T. and T.H. performed cell culture experiments. A.G. provided small molecules. E.A.M. and D.A.P. wrote the paper, with input from T.K.T., T.H. and S.A.K. \n\nThe authors declare no competing interests.\n\nPublished - s41598-019-48914-7.pdf
Supplemental Material - 41598_2019_48914_MOESM1_ESM.pdf
", "abstract": "The circadian clock ensures that behavioral and physiological processes occur at appropriate times during the 24-hour day/night cycle, and is regulated at both the cellular and organismal levels. To identify pathways acting on intact animals, we performed a small molecule screen using a luminescent reporter of molecular circadian rhythms in zebrafish larvae. We identified both known and novel pathways that affect circadian period, amplitude and phase. Several drugs identified in the screen did not affect circadian rhythms in cultured cells derived from luminescent reporter embryos or in established zebrafish and mammalian cell lines, suggesting they act via mechanisms absent in cell culture. Strikingly, using drugs that promote or inhibit inflammation, as well as a mutant that lacks microglia, we found that inflammatory state affects circadian amplitude. These results demonstrate a benefit of performing drug screens using intact animals and provide novel targets for treating circadian rhythm disorders.", "date": "2019-08-27", "date_type": "published", "publication": "Scientific Reports", "volume": "9", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 12405", "id_number": "CaltechAUTHORS:20190827-104428064", "issn": "2045-2322", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190827-104428064", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "NS070911" }, { "agency": "NIH", "grant_number": "NS101158" }, { "agency": "NIH", "grant_number": "NS095824" }, { "agency": "NIH", "grant_number": "NS101665" }, { "agency": "Sanofi-Aventis" }, { "agency": "Japan Society for the Promotion of Science (JSPS)", "grant_number": "15H05590" } ] }, "doi": "10.1038/s41598-019-48914-7", "pmcid": "PMC6712016", "primary_object": { "basename": "41598_2019_48914_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/68z2a-3w124/files/41598_2019_48914_MOESM1_ESM.pdf" }, "related_objects": [ { "basename": "s41598-019-48914-7.pdf", "url": "https://authors.library.caltech.edu/records/68z2a-3w124/files/s41598-019-48914-7.pdf" } ], "resource_type": "article", "pub_year": "2019", "author_list": "Mosser, Eric A.; Chiu, Cindy N.; et el." }, { "id": "https://authors.library.caltech.edu/records/tvp5y-12b43", "eprint_id": 96666, "eprint_status": "archive", "datestamp": "2023-08-22 02:18:23", "lastmod": "2023-10-20 21:25:04", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Oikonomou-Grigorios", "name": { "family": "Oikonomou", "given": "Grigorios" }, "orcid": "0000-0001-6797-7375" }, { "id": "Altermatt-Michael", "name": { "family": "Altermatt", "given": "Michael" }, "orcid": "0000-0003-2841-5374" }, { "id": "Zhang-Rong-wei", "name": { "family": "Zhang", "given": "Rong-wei" }, "orcid": "0000-0003-1145-8589" }, { "id": "Coughlin-Gerard-M", "name": { "family": "Coughlin", "given": "Gerard M." } }, { "id": "Montz-Christin", "name": { "family": "Montz", "given": "Christin" } }, { "id": "Gradinaru-V", "name": { "family": "Gradinaru", "given": "Viviana" }, "orcid": "0000-0001-5868-348X" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "The Serotonergic Raphe Promote Sleep in Zebrafish and Mice", "ispublished": "pub", "full_text_status": "public", "keywords": "sleep; arousal; serotonin; 5-HT; raphe; optogenetics; fiber photometry", "note": "\u00a9 2019 Elsevier Inc. \n\nReceived 20 September 2018, Revised 11 April 2019, Accepted 22 May 2019, Available online 24 June 2019. \n\nData and Code Availability: The datasets generated and analyzed in this study are available from the corresponding author upon request. \n\nWe thank the Gradinaru and Prober labs for helpful discussions; Viveca Sapin, Uyen Pham, Hannah Hurley, and Tasha Cammidge for zebrafish husbandry assistance; Chanpreet Singh for generating the Tg(aanat2:ChR2-YFP) line; Elisha D. Mackey for supervising mouse breeding; Andres Collazo for advice on 2-photon laser ablation; Justin S. Bois for advice on statistics; and Catherine M. Oikonomou for critical reading of the manuscript. This work was supported by the NIH (F32NS082010 to G.O.; NIH BRAIN RF1MH117069 to V.G.; and R01NS070911, R01NS101158, R01NS095824, and R01NS101665 to D.A.P.), Center for Molecular and Cellular Neuroscience of the Chen Institute (to V.G.) and the Beckman Institute for CLARITY, Optogenetics and Vector Engineering Research (to V.G.). G.M.C. is supported by a PGS-D from the National Science and Engineering Research Council (NSERC) of Canada. V.G. is a Heritage Principal Investigator supported by the Heritage Medical Research Institute. \n\nAuthor Contributions: G.O., M.A., D.A.P., and V.G. designed experiments. G.O. performed zebrafish experiments. M.A. performed mouse experiments. R.Z. performed zebrafish electrophysiology. G.M.C. performed mouse histology and quantification. C.M. isolated the zebrafish tph2 promoter. V.G. supervised rodent aspects of the project. D.A.P. supervised zebrafish aspects of the project. G.O., M.A., V.G., and D.A.P. wrote the paper with input from R.Z. and G.M.C. \n\nThe authors declare no competing interests.\n\nAccepted Version - nihms-1530614.pdf
Supplemental Material - 1-s2.0-S089662731930491X-mmc1.pdf
", "abstract": "The role of serotonin (5-HT) in sleep is controversial: early studies suggested a sleep-promoting role, but eventually the paradigm shifted toward a wake-promoting function for the serotonergic raphe. Here, we provide evidence from zebrafish and mice that the raphe are critical for the initiation and maintenance of sleep. In zebrafish, genetic ablation of 5-HT production by the raphe reduces sleep, sleep depth, and the homeostatic response to sleep deprivation. Pharmacological inhibition or ablation of the raphe reduces sleep, while optogenetic stimulation increases sleep. Similarly, in mice, ablation of the raphe increases wakefulness and impairs the homeostatic response to sleep deprivation, whereas tonic optogenetic stimulation at a rate similar to baseline activity induces sleep. Interestingly, burst optogenetic stimulation induces wakefulness in accordance with previously described burst activity of the raphe during arousing stimuli. These results indicate that the serotonergic system promotes sleep in both diurnal zebrafish and nocturnal rodents.", "date": "2019-08-21", "date_type": "published", "publication": "Neuron", "volume": "103", "number": "4", "publisher": "Cell Press", "pagerange": "686-701", "id_number": "CaltechAUTHORS:20190624-113552525", "issn": "0896-6273", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190624-113552525", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32NS082010" }, { "agency": "NIH", "grant_number": "RF1MH117069" }, { "agency": "NIH", "grant_number": "R01NS070911" }, { "agency": "NIH", "grant_number": "R01NS101158" }, { "agency": "NIH", "grant_number": "R01NS095824" }, { "agency": "NIH", "grant_number": "R01NS101665" }, { "agency": "Tianqiao and Chrissy Chen Institute for Neuroscience" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" }, { "agency": "Heritage Medical Research Institute" } ] }, "local_group": { "items": [ { "id": "Heritage-Medical-Research-Institute" }, { "id": "Tianqiao-and-Chrissy-Chen-Institute-for-Neuroscience" } ] }, "doi": "10.1016/j.neuron.2019.05.038", "pmcid": "PMC6706304", "primary_object": { "basename": "1-s2.0-S089662731930491X-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/tvp5y-12b43/files/1-s2.0-S089662731930491X-mmc1.pdf" }, "related_objects": [ { "basename": "nihms-1530614.pdf", "url": "https://authors.library.caltech.edu/records/tvp5y-12b43/files/nihms-1530614.pdf" } ], "resource_type": "article", "pub_year": "2019", "author_list": "Oikonomou, Grigorios; Altermatt, Michael; et el." }, { "id": "https://authors.library.caltech.edu/records/ev4wc-e3x68", "eprint_id": 97709, "eprint_status": "archive", "datestamp": "2023-08-22 02:15:02", "lastmod": "2023-10-18 16:38:47", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ruzzo-E-K", "name": { "family": "Ruzzo", "given": "Elizabeth K." } }, { "id": "P\u00e9rez-Cano-L", "name": { "family": "P\u00e9rez-Cano", "given": "Laura" } }, { "id": "Jung-Jae-Yoon", "name": { "family": "Jung", "given": "Jae-Yoon" } }, { "id": "Wang-Lee-kai", "name": { "family": "Wang", "given": "Lee-kai" } }, { "id": "Kashef-Haghighi-D", "name": { "family": "Kashef-Haghighi", "given": "Dorna" } }, { "id": "Hartl-C", "name": { "family": "Hartl", "given": "Chris" } }, { "id": "Singh-C", "name": { "family": "Singh", "given": "Chanpreet" }, "orcid": "0000-0002-2697-3033" }, { "id": "Xu-Jin", "name": { "family": "Xu", "given": "Jin" } }, { "id": "Hoekstra-J-N", "name": { "family": "Hoekstra", "given": "Jackson N." } }, { "id": "Leventhal-O", "name": { "family": "Leventhal", "given": "Olivia" } }, { "id": "Lepp\u00e4-V-M", "name": { "family": "Lepp\u00e4", "given": "Virpi M." } }, { "id": "Gandal-M-J", "name": { "family": "Gandal", "given": "Michael J." } }, { "id": "Paskov-K", "name": { "family": "Paskov", "given": "Kelley" } }, { "id": "Stockham-N", "name": { "family": "Stockham", "given": "Nate" } }, { "id": "Polioudakis-D", "name": { "family": "Polioudakis", "given": "Damon" } }, { "id": "Lowe-J-K", "name": { "family": "Lowe", "given": "Jennifer K." } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Geschwind-D-H", "name": { "family": "Geschwind", "given": "Daniel H." }, "orcid": "0000-0003-2896-3450" }, { "id": "Wall-D-P", "name": { "family": "Wall", "given": "Dennis P." } } ] }, "title": "Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks", "ispublished": "pub", "full_text_status": "public", "keywords": "genetics; autism; ASD; multiplex families; machine learning; inherited; de novo", "note": "\u00a9 2019 Elsevier. \n\nReceived 15 November 2018, Revised 8 April 2019, Accepted 11 July 2019, Available online 8 August 2019. \n\nWe thank Stephanie A. Arteaga, Stephanie N. Kravitz, Cheyenne L. Schloffman, Min Sun, Tor Solli-Nowlan, T. Chang, Hyejung Won, Sasha Sharma, Marlena Duda, Greg Madden McInnes, Ravina Jain, Valent\u00ed Moncunill, Josep M. Mercader, Montserrat Puiggr\u00f2s, Hailey H. Choi, Anika Gupta, and David Torrents for technical support and Hannah Hurley and Amina Kinkhabwala for assistance with zebrafish experiments. We are grateful to The Hartwell Foundation for supporting the creation of the iHART database. We are grateful to the Simons Foundation for additional support for genome sequencing. We are grateful to the PRACE Research Infrastructure resource MareNostrum III based in Spain at the Barcelona Supercomputing Center. We thank the New York Genome Center for conducting sequencing and initial quality control. We thank A. Gordon, J. Huang, J. Sebat, and D. Antaki for help with resolving the DLG2 structural variant. We thank Amazon Web Services for their grant support for the computational infrastructure and storage for the iHART database. We thank J. Sul for helpful discussions and for suggesting a machine learning approach. This work has been supported by grants from The Hartwell Foundation and the NIH (U24MH081810, R01MH064547, NS101158, NS070911, NS101665, NS095824, S10OD011939, P30AG10161, R01AG17917, and U01AG61356) and from the Stanford Precision Health and Integrated Diagnostics Center and from the Stanford Bio-X Center. We are grateful to all of the families at the participating SSC sites as well as the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, R. Goin-Kochel, E. Hanson, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, K. Pelphrey, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, Z. Warren, and E. Wijsman). We appreciate obtaining access to genetic data on SFARI Base. Approved researchers can obtain the SSC population dataset described in this study (https://www.sfari.org/2015/12/11/whole-genome-analysis-of-the-simons-simplex-collection-ssc-2/#chapter-wgs-of-500-additional-ssc-families) by applying at https://base.sfari.org. \n\nAuthor Contributions: E.K.R. and L.P.C. contributed to the analytical plans, performed analyses, and interpreted results. J.K.L. selected and submitted samples for sequencing. E.K.R., J.Y.J., L.K.W., and J.K.L. performed quality control checks. L.K.W. wrote scripts for data processing and helped interpret results. L.P.C., D.K.H., J.Y.J., E.K.R., and D.P.W. developed ARC. C.H. interpreted results and ran TADA simulations. E.K.R. and C.H. ran high-risk inherited simulations. J.Y.J. and D.P.W. designed the access systems. J.Y.J. performed joint genotyping, VCF annotation, and data transfers. L.P.C. and D.K.H. processed SVs, and L.P.C. wrote the SV cross-algorithm comparison pipeline. D.P. performed single-cell analyses. M.J.G. analyzed phenotypes. V.M.L. helped with array-based CNV analyses. C.S., J.X., and D.A.P. performed and analyzed zebrafish experiments. D.P.W. identified and supplied funding. E.K.R. and D.H.G. took the lead in writing the manuscript, and all authors reviewed, edited, and approved the manuscript. D.H.G. and D.P.W. supervised the experimental design and analysis and interpreted results. \n\nData and Code Availability: The whole-genome sequencing data generated during this study are available from the Hartwell Foundation's Autism Research and Technology Initiative (iHART) following request and approval of the data use agreement available at http://www.ihart.org. Access to the whole-genome sequencing data generated in this study will be subject to approval by Autism Speaks and AGRE. Details about the format of the data, access options, and access instructions are included at http://www.ihart.org. \n\nWe also freely provide the code for ARC (Artifact Removal by Classifier), our random forest supervised model developed to distinguish true rare de novo variants from LCL-specific genetic aberrations or other types of artifacts such as sequencing and mapping errors, together with a full tutorial at https://github.com/walllab/iHART-ARC. \n\nInteractive genotype/phenotype search engine: To facilitate sharing of iHART data with the broader autism research community and patients, we implemented a set of online data access methods to preview and search genetic variants and phenotypic traits (http://www.ihart.org/home). \n\nZebrafish data: The zebrafish datasets generated and analyzed in this study, and the code used to generate the data, are available upon request. \n\nThe authors declare no competing interests.\n\nSupplemental Material - 1-s2.0-S0092867419307809-mmc1.xlsx
Supplemental Material - 1-s2.0-S0092867419307809-mmc2.xlsx
Supplemental Material - 1-s2.0-S0092867419307809-mmc3.xlsx
Supplemental Material - 1-s2.0-S0092867419307809-mmc4.xlsx
Supplemental Material - 1-s2.0-S0092867419307809-mmc5.xlsx
", "abstract": "We performed a comprehensive assessment of rare inherited variation in autism spectrum disorder (ASD) by analyzing whole-genome sequences of 2,308 individuals from families with multiple affected children. We implicate 69 genes in ASD risk, including 24 passing genome-wide Bonferroni correction and 16 new ASD risk genes, most supported by rare inherited variants, a substantial extension of previous findings. Biological pathways enriched for genes harboring inherited variants represent cytoskeletal organization and ion transport, which are distinct from pathways implicated in previous studies. Nevertheless, the de novo and inherited genes contribute to a common protein-protein interaction network. We also identified structural variants (SVs) affecting non-coding regions, implicating recurrent deletions in the promoters of DLG2 and NR3C2. Loss of nr3c2 function in zebrafish disrupts sleep and social function, overlapping with human ASD-related phenotypes. These data support the utility of studying multiplex families in ASD and are available through the Hartwell Autism Research and Technology portal.", "date": "2019-08-08", "date_type": "published", "publication": "Cell", "volume": "178", "number": "4", "publisher": "Elsevier", "pagerange": "850-866", "id_number": "CaltechAUTHORS:20190808-135241284", "issn": "0092-8674", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190808-135241284", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Hartwell Foundation" }, { "agency": "NIH", "grant_number": "U24 MH081810" }, { "agency": "NIH", "grant_number": "R01MH064547" }, { "agency": "NIH", "grant_number": "NS101158" }, { "agency": "NIH", "grant_number": "NS070911" }, { "agency": "NIH", "grant_number": "NS101665" }, { "agency": "NIH", "grant_number": "NS095824" }, { "agency": "NIH", "grant_number": "S10OD011939" }, { "agency": "NIH", "grant_number": "P30AG10161" }, { "agency": "NIH", "grant_number": "R01AG17917" }, { "agency": "NIH", "grant_number": "U01AG61356" }, { "agency": "Stanford Precision Health and Integrated Diagnostics Center" }, { "agency": "Stanford Bio-X Center" } ] }, "doi": "10.1016/j.cell.2019.07.015", "pmcid": "PMC7102900", "primary_object": { "basename": "1-s2.0-S0092867419307809-mmc5.xlsx", "url": "https://authors.library.caltech.edu/records/ev4wc-e3x68/files/1-s2.0-S0092867419307809-mmc5.xlsx" }, "related_objects": [ { "basename": "1-s2.0-S0092867419307809-mmc1.xlsx", "url": "https://authors.library.caltech.edu/records/ev4wc-e3x68/files/1-s2.0-S0092867419307809-mmc1.xlsx" }, { "basename": "1-s2.0-S0092867419307809-mmc2.xlsx", "url": "https://authors.library.caltech.edu/records/ev4wc-e3x68/files/1-s2.0-S0092867419307809-mmc2.xlsx" }, { "basename": "1-s2.0-S0092867419307809-mmc3.xlsx", "url": "https://authors.library.caltech.edu/records/ev4wc-e3x68/files/1-s2.0-S0092867419307809-mmc3.xlsx" }, { "basename": "1-s2.0-S0092867419307809-mmc4.xlsx", "url": "https://authors.library.caltech.edu/records/ev4wc-e3x68/files/1-s2.0-S0092867419307809-mmc4.xlsx" } ], "resource_type": "article", "pub_year": "2019", "author_list": "Ruzzo, Elizabeth K.; P\u00e9rez-Cano, Laura; et el." }, { "id": "https://authors.library.caltech.edu/records/h3qgk-km605", "eprint_id": 96110, "eprint_status": "archive", "datestamp": "2023-08-22 01:47:22", "lastmod": "2023-10-20 20:52:13", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhang-Rong-wei", "name": { "family": "Zhang", "given": "Rong-wei" }, "orcid": "0000-0003-1145-8589" }, { "id": "Du-Wen-jie", "name": { "family": "Du", "given": "Wen-jie" } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Du-Jiu-lin", "name": { "family": "Du", "given": "Jiu-lin" } } ] }, "title": "M\u00fcller Glial Cells Participate in Retinal Waves via Glutamate Transporters and AMPA Receptors", "ispublished": "pub", "full_text_status": "public", "keywords": "retinal wave; M\u00fcller glial cell; glutamate transporter; AMPA receptor; zebrafish", "note": "\u00a9 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). \n\nReceived 23 July 2018, Revised 21 February 2019, Accepted 30 April 2019, Available online 4 June 2019. \n\nWe are grateful to Dr. Pamela A. Raymond for providing the Tg(GFAP:eGFP) line and to Dr. Xiaoquan Li for making the Tg(GFAP:GCaMP2) line. This work was supported by the National Natural Science Foundation of China (31771144), the Key Research Program of Frontier Sciences (QYZDY-SSW-SMC028), the Strategic Priority Research Program (XDB32010200), the Youth Innovation Promotion Association of Chinese Academy of Sciences, Shanghai Municipal Science and Technology Major Project (18JC1410100 and 2018SHZDZX05), the China Wan-Ren Program, and the Shanghai Leading Scientist Program. The ORCID for R.-W.Z. is 0000-0003-1145-8589. \n\nAuthor Contributions: R.-W.Z. and J.-L.D. conceived the project and designed the experiments. R.-W.Z. and W.-J.D. performed the research and analyzed the data. D.A.P. provided some experimental reagents. R.-W.Z. and J.-L.D. wrote the paper. \n\nThe authors declare no competing interests.\n\nPublished - 1-s2.0-S2211124719306229-main.pdf
Accepted Version - nihms-1534459.pdf
Supplemental Material - 1-s2.0-S2211124719306229-mmc1.pdf
", "abstract": "Retinal waves, the spontaneous patterned neural activities propagating among developing retinal ganglion cells (RGCs), instruct the activity-dependent refinement of visuotopic maps. Although it is known that the wave is initiated successively by amacrine cells and bipolar cells, the behavior and function of glia in retinal waves remain unclear. Using multiple in vivo methods in larval zebrafish, we found that M\u00fcller glial cells (MGCs) display wave-like spontaneous activities, which start at MGC processes within the inner plexiform layer, vertically spread to their somata and endfeet, and horizontally propagate into neighboring MGCs. MGC waves depend on glutamatergic signaling derived from bipolar cells. Moreover, MGCs express both glia-specific glutamate transporters and the AMPA subtype of glutamate receptors. The AMPA receptors mediate MGC calcium activities during retinal waves, whereas the glutamate transporters modulate the occurrence of retinal waves. Thus, MGCs can sense and regulate retinal waves via AMPA receptors and glutamate transporters, respectively.", "date": "2019-06-04", "date_type": "published", "publication": "Cell Reports", "volume": "27", "number": "10", "publisher": "Cell Press", "pagerange": "2871-2880", "id_number": "CaltechAUTHORS:20190604-111311920", "issn": "2211-1247", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190604-111311920", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "National Natural Science Foundation of China", "grant_number": "31771144" }, { "agency": "Key Research Program of Frontier Sciences", "grant_number": "QYZDY-SSW-SMC028" }, { "agency": "Strategic Priority Research Program", "grant_number": "XDB32010200" }, { "agency": "Chinese Academy of Sciences" }, { "agency": "Shanghai Municipal Science and Technology Major Project", "grant_number": "18JC1410100" }, { "agency": "Shanghai Municipal Science and Technology Major Project", "grant_number": "2018SHZDZX05" }, { "agency": "China Wan-Ren Program" }, { "agency": "Shanghai Leading Scientist Program" } ] }, "doi": "10.1016/j.celrep.2019.05.011", "pmcid": "PMC6659749", "primary_object": { "basename": "1-s2.0-S2211124719306229-main.pdf", "url": "https://authors.library.caltech.edu/records/h3qgk-km605/files/1-s2.0-S2211124719306229-main.pdf" }, "related_objects": [ { "basename": "1-s2.0-S2211124719306229-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/h3qgk-km605/files/1-s2.0-S2211124719306229-mmc1.pdf" }, { "basename": "nihms-1534459.pdf", "url": "https://authors.library.caltech.edu/records/h3qgk-km605/files/nihms-1534459.pdf" } ], "resource_type": "article", "pub_year": "2019", "author_list": "Zhang, Rong-wei; Du, Wen-jie; et el." }, { "id": "https://authors.library.caltech.edu/records/hnsyn-hsb54", "eprint_id": 94371, "eprint_status": "archive", "datestamp": "2023-08-22 01:19:47", "lastmod": "2023-10-20 17:54:48", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Fontenas-Laura", "name": { "family": "Fontenas", "given": "Laura" } }, { "id": "Welsh-Taylor-G", "name": { "family": "Welsh", "given": "Taylor G." } }, { "id": "Piller-Melanie", "name": { "family": "Piller", "given": "Melanie" } }, { "id": "Coughenour-Patricia", "name": { "family": "Coughenour", "given": "Patricia" } }, { "id": "Gandhi-Avni-V", "name": { "family": "Gandhi", "given": "Avni V." } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Kucenas-Sarah", "name": { "family": "Kucenas", "given": "Sarah" } } ] }, "title": "The Neuromodulator Adenosine Regulates Oligodendrocyte Migration at Motor Exit Point Transition Zones", "ispublished": "pub", "full_text_status": "public", "keywords": "oligodendrocyte progenitor cell; motor exit point glia; motor exit point transition zone; migration; adenosine; neural activity; zebrafish", "note": "\u00a9 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). \n\nReceived 5 January 2018, Revised 27 January 2019, Accepted 2 March 2019, Available online 2 April 2019. \n\nWe would like to thank Drs. John Lazo and Elizabeth Sharlow for the LOPAC^(1280) library and for advice on designing the chemical screen. We thank Dr. Marcel Tawk for providing the pGEMTEZ-TeTxLC plasmid and Dr. Cody Smith for the UAS:GCaMP5 plasmid. We are extremely grateful to Lori Tocke for care and maintenance of the zebrafish facility and to all the members of the Kucenas lab and Dr. Dave Parichy for helpful comments and advice. This work was funded by the NIH through grants NS072212 and NS092070 (S.K.), NS070911 (D.A.P.), and NS101665 (D.A.P.) and by The Hartwell Foundation (S.K.). \n\nAuthor Contributions: L.F., T.G.W., and S.K. conceived the study, and L.F., T.G.W., M.P., and P.C. conducted and analyzed all of the experiments. A.V.G. and D.A.P. created the adora2aa TALEN mutant line. L.F., T.G.W., and S.K. wrote the manuscript with input from D.A.P. \n\nThe authors declare no competing interests.\n\nPublished - 1-s2.0-S2211124719303201-main.pdf
Accepted Version - nihms-1526190.pdf
Supplemental Material - 1-s2.0-S2211124719303201-mmc1.pdf
", "abstract": "During development, oligodendrocyte progenitor cells (OPCs) migrate extensively throughout the spinal cord. However, their migration is restricted at transition zones (TZs). At these specialized locations, unique glial cells in both zebrafish and mice play a role in preventing peripheral OPC migration, but the mechanisms of this regulation are not understood. To elucidate the mechanisms that mediate OPC segregation at motor exit point (MEP) TZs, we performed an unbiased small-molecule screen. Using chemical screening and in vivo imaging, we discovered that inhibition of A2a adenosine receptors (ARs) causes ectopic OPC migration out of the spinal cord. We provide in vivo evidence that neuromodulation, partially mediated by adenosine, influences OPC migration specifically at the MEP TZ. This work opens exciting possibilities for understanding how OPCs reach their final destinations during development and identifies mechanisms that could promote their migration in disease.", "date": "2019-04-02", "date_type": "published", "publication": "Cell Reports", "volume": "27", "number": "1", "publisher": "Cell Press", "pagerange": "115-128", "id_number": "CaltechAUTHORS:20190402-133417265", "issn": "2211-1247", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190402-133417265", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "NS072212" }, { "agency": "NIH", "grant_number": "NS092070" }, { "agency": "NIH", "grant_number": "NS070911" }, { "agency": "NIH", "grant_number": "NS101665" }, { "agency": "Hartwell Foundation" } ] }, "doi": "10.1016/j.celrep.2019.03.013", "pmcid": "PMC6461400", "primary_object": { "basename": "1-s2.0-S2211124719303201-main.pdf", "url": "https://authors.library.caltech.edu/records/hnsyn-hsb54/files/1-s2.0-S2211124719303201-main.pdf" }, "related_objects": [ { "basename": "1-s2.0-S2211124719303201-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/hnsyn-hsb54/files/1-s2.0-S2211124719303201-mmc1.pdf" }, { "basename": "nihms-1526190.pdf", "url": "https://authors.library.caltech.edu/records/hnsyn-hsb54/files/nihms-1526190.pdf" } ], "resource_type": "article", "pub_year": "2019", "author_list": "Fontenas, Laura; Welsh, Taylor G.; et el." }, { "id": "https://authors.library.caltech.edu/records/e07cv-ac915", "eprint_id": 92557, "eprint_status": "archive", "datestamp": "2023-08-19 14:12:28", "lastmod": "2023-10-20 15:51:01", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Oikonomou-G", "name": { "family": "Oikonomou", "given": "Grigorios" }, "orcid": "0000-0001-6797-7375" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Linking immunity and sickness-induced sleep", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 American Association for the Advancement of Science.\n\nAccepted Version - nihms-1040683.pdf
", "abstract": "We are all familiar with the sleepiness experienced during sickness. What is less often appreciated is that this increased need for sleep is caused by the release of signaling molecules by our own immune and nervous systems, and not by the infectious agents themselves (1). Indeed, for the spread of a virus or a bacterium, it would be much better if we were out and about when sick, instead of sleeping. On page 509 of this issue, Toda et al. (2) reveal another facet of the interplay between sleep and immunity by identifying NEMURI (NUR), an antimicrobial peptide (AMP) produced by the fruit fly Drosophila melanogaster that also has sleep-promoting properties. Because humans synthesize more than 100 different AMPs (3), this work could have implications for interactions between sleep and immunity during human disease.", "date": "2019-02-01", "date_type": "published", "publication": "Science", "volume": "363", "number": "6426", "publisher": "American Association for the Advancement of Science", "pagerange": "455-456", "id_number": "CaltechAUTHORS:20190201-092224086", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190201-092224086", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1126/science.aaw2113", "pmcid": "PMC6628894", "primary_object": { "basename": "nihms-1040683.pdf", "url": "https://authors.library.caltech.edu/records/e07cv-ac915/files/nihms-1040683.pdf" }, "resource_type": "article", "pub_year": "2019", "author_list": "Oikonomou, Grigorios and Prober, David A." }, { "id": "https://authors.library.caltech.edu/records/834wx-wz138", "eprint_id": 84781, "eprint_status": "archive", "datestamp": "2023-08-19 07:45:43", "lastmod": "2023-10-20 21:50:32", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Jaggard-J-B", "name": { "family": "Jaggard", "given": "James B." }, "orcid": "0000-0003-4091-9946" }, { "id": "Stahl-B-A", "name": { "family": "Stahl", "given": "Bethany A." }, "orcid": "0000-0001-9218-2996" }, { "id": "Lloyd-E", "name": { "family": "Lloyd", "given": "Evan" } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Duboue-E-R", "name": { "family": "Duboue", "given": "Erik R." }, "orcid": "0000-0003-3303-5149" }, { "id": "Keene-A-C", "name": { "family": "Keene", "given": "Alex C." }, "orcid": "0000-0001-6118-5537" } ] }, "title": "Hypocretin underlies the evolution of sleep loss in the Mexican cavefish", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2018 Copyright Jaggard et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.eLife Sciences Publications Ltd. \n\nReceived: 10 October 2017. Accepted: 25 November 2017. Published: 06 February 2018. \n\nReviewing editor: Marianne Bronner, California Institute of Technology, United States \n\nThis work was funded by National Science Foundation Award IOS-125762 to ACK. The authors are grateful to Masato Yoshizawa (Hawai'i) for technical guidance and the Department of Comparative Medicine at FAU for support maintaining the fish facility. \n\nThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. \n\nAuthor contributions: James B Jaggard, Conceptualization, Data curation, Formal analysis, Investigation, Methodology,\nWriting\u2014original draft, Writing\u2014review and editing; Bethany A Stahl, Conceptualization, Formal\nanalysis, Investigation, Writing\u2014original draft, Writing\u2014review and editing; Evan Lloyd, Formal anal-\nysis, Investigation, Methodology, Writing\u2014original draft, Writing\u2014review and editing; David A\nProber, Conceptualization, Resources, Validation, Writing\u2014original draft, Writing\u2014review and edit-\ning; Erik R Duboue, Conceptualization, Resources, Software, Formal analysis, Visualization, Method-\nology, Writing\u2014original draft, Writing\u2014review and editing; Alex C Keene, Conceptualization,\nSupervision, Funding acquisition, Visualization, Writing\u2014original draft, Project administration, Writing\u2014review and editing \n\nThe authors declare that no competing interests exist.\n\nPublished - elife-32637-v1.pdf
Submitted - 122903.full.pdf
", "abstract": "The duration of sleep varies dramatically between species, yet little is known about the genetic basis or evolutionary factors driving this variation in behavior. The Mexican cavefish, Astyanax mexicanus, exists as surface populations that inhabit rivers, and multiple cave populations with convergent evolution on sleep loss. The number of Hypocretin/Orexin (HCRT)-positive hypothalamic neurons is increased significantly in cavefish, and HCRT is upregulated at both the transcript and protein levels. Pharmacological or genetic inhibition of HCRT signaling increases sleep in cavefish, suggesting enhanced HCRT signaling underlies the evolution of sleep loss. Ablation of the lateral line or starvation, manipulations that selectively promote sleep in cavefish, inhibit hcrt expression in cavefish while having little effect on surface fish. These findings provide the first evidence of genetic and neuronal changes that contribute to the evolution of sleep loss, and support a conserved role for HCRT in sleep regulation.", "date": "2018-02-06", "date_type": "published", "publication": "eLife", "volume": "7", "publisher": "eLife Sciences Publications", "pagerange": "Art. No. 32637", "id_number": "CaltechAUTHORS:20180212-084202846", "issn": "2050-084X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180212-084202846", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "IOS-125762" } ] }, "doi": "10.7554/eLife.32637.001", "pmcid": "PMC5800846", "primary_object": { "basename": "122903.full.pdf", "url": "https://authors.library.caltech.edu/records/834wx-wz138/files/122903.full.pdf" }, "related_objects": [ { "basename": "elife-32637-v1.pdf", "url": "https://authors.library.caltech.edu/records/834wx-wz138/files/elife-32637-v1.pdf" } ], "resource_type": "article", "pub_year": "2018", "author_list": "Jaggard, James B.; Stahl, Bethany A.; et el." }, { "id": "https://authors.library.caltech.edu/records/5f0fe-7qb60", "eprint_id": 84785, "eprint_status": "archive", "datestamp": "2023-08-21 22:41:56", "lastmod": "2023-10-18 16:41:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Discovery of Hypocretin/Orexin Ushers in a New Era of Sleep Research", "ispublished": "pub", "full_text_status": "public", "keywords": "sleep; arousal; hypocretin; orexin", "note": "\u00a9 2017 Elsevier Ltd. \n\nAvailable online 6 February 2018.\n\nAccepted Version - nihms923184.pdf
", "abstract": "Prior to the 21st century, genetic mechanisms that regulate sleep were largely unknown. In 1998, de Lecea et al. [1] (Proc. Natl. Acad. Sci. U. S. A. 1998; 95:322\u2013327) and Sakurai et al. [2] (Cell 1998; 92: 573\u2013585) reported the discovery of a gene they named hypocretin and orexin, respectively, which led to a revolution in our understanding of genetic and neuronal mechanisms that regulate sleep.", "date": "2018-02", "date_type": "published", "publication": "Trends in Neurosciences", "volume": "41", "number": "2", "publisher": "Elsevier", "pagerange": "70-72", "id_number": "CaltechAUTHORS:20180212-094508465", "issn": "0166-2236", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180212-094508465", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1016/j.tins.2017.11.007", "pmcid": "PMC5805467", "primary_object": { "basename": "nihms923184.pdf", "url": "https://authors.library.caltech.edu/records/5f0fe-7qb60/files/nihms923184.pdf" }, "resource_type": "article", "pub_year": "2018", "author_list": "Prober, David A." }, { "id": "https://authors.library.caltech.edu/records/0e30z-0gk72", "eprint_id": 83754, "eprint_status": "archive", "datestamp": "2023-08-21 22:24:20", "lastmod": "2023-10-17 23:28:55", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Singh-Chanpreet", "name": { "family": "Singh", "given": "Chanpreet" }, "orcid": "0000-0002-2697-3033" }, { "id": "Rihel-Jason", "name": { "family": "Rihel", "given": "Jason" }, "orcid": "0000-0003-4067-2066" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Neuropeptide Y Regulates Sleep by Modulating Noradrenergic Signaling", "ispublished": "pub", "full_text_status": "public", "keywords": "sleep; neuropeptide Y; hypothalamus; locus coeruleus; noradrenaline; locomotor activity; arousal; genetics; zebrafish", "note": "\u00a9 2017 Elsevier Ltd. \n\nReceived 31 March 2017, Revised 11 October 2017, Accepted 6 November 2017, Available online 7 December 2017. \n\nData and Software Availability: Custom PERL and MATLAB code used for zebrafish behavioral analysis is available upon request. \n\nWe thank Daisy Chilin, Alex Mack Cruz, Axel Dominguez, and Kenna Molinder for animal husbandry assistance; Viveca Sapin and Uyen Pham for genotyping assistance; Owen Randlett, Ulrich Herget, Caroline Wee, and Marcus Ghosh for assistance with Z-Brain registration; and Grigorios Oikonomou for comments on the manuscript. This work was supported by grants from the NIH (NS070911, NS101665, NS095824, and NS101158 to D.A.P.), the Mallinckrodt, Rita Allen, and Brain and Behavior Research foundations (to D.A.P.), and a UCL Excellence Fellowship and European Research Council Starting Grant (282027 to J.R.). \n\nAuthor Contributions: D.A.P. and J.R. performed the genetic screen. C.S. and D.A.P. conceptualized and designed the experiments and generated reagents. C.S. performed the experiments and analyzed the data. C.S. and D.A.P. wrote the paper with assistance from J.R. D.A.P. supervised the project.\n\nAccepted Version - nihms919667.pdf
Supplemental Material - mmc1.pdf
Supplemental Material - mmc2.mp4
Supplemental Material - mmc3.mp4
", "abstract": "Sleep is an essential and evolutionarily conserved behavioral state whose regulation remains poorly understood. To identify genes that regulate vertebrate sleep, we recently performed a genetic screen in zebrafish, and here we report the identification of neuropeptide Y (NPY) as both necessary for normal daytime sleep duration and sufficient to promote sleep. We show that overexpression of NPY increases sleep, whereas mutation of npy or ablation of npy-expressing neurons decreases sleep. By analyzing sleep architecture, we show that NPY regulates sleep primarily by modulating the length of wake bouts. To determine how NPY regulates sleep, we tested for interactions with several systems known to regulate sleep, and provide anatomical, molecular, genetic, and pharmacological evidence that NPY promotes sleep by inhibiting noradrenergic signaling. These data establish NPY as an important vertebrate sleep/wake regulator and link NPY signaling to an established arousal-promoting system.", "date": "2017-12-18", "date_type": "published", "publication": "Current Biology", "volume": "27", "number": "24", "publisher": "Cell Press", "pagerange": "3796-3811", "id_number": "CaltechAUTHORS:20171208-111531827", "issn": "0960-9822", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171208-111531827", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "NS070911" }, { "agency": "NIH", "grant_number": "NS101665" }, { "agency": "NIH", "grant_number": "NS095824" }, { "agency": "NIH", "grant_number": "NS101158" }, { "agency": "Mallinckrodt Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Brain and Behavior Research Foundation" }, { "agency": "University College London" }, { "agency": "European Research Council (ERC)", "grant_number": "82027" } ] }, "local_group": { "items": [ { "id": "Tianqiao-and-Chrissy-Chen-Institute-for-Neuroscience" } ] }, "doi": "10.1016/j.cub.2017.11.018", "pmcid": "PMC5736401", "primary_object": { "basename": "nihms919667.pdf", "url": "https://authors.library.caltech.edu/records/0e30z-0gk72/files/nihms919667.pdf" }, "related_objects": [ { "basename": "mmc1.pdf", "url": "https://authors.library.caltech.edu/records/0e30z-0gk72/files/mmc1.pdf" }, { "basename": "mmc2.mp4", "url": "https://authors.library.caltech.edu/records/0e30z-0gk72/files/mmc2.mp4" }, { "basename": "mmc3.mp4", "url": "https://authors.library.caltech.edu/records/0e30z-0gk72/files/mmc3.mp4" } ], "resource_type": "article", "pub_year": "2017", "author_list": "Singh, Chanpreet; Rihel, Jason; et el." }, { "id": "https://authors.library.caltech.edu/records/0e1n9-pqz42", "eprint_id": 82209, "eprint_status": "archive", "datestamp": "2023-08-21 22:14:29", "lastmod": "2023-10-23 15:51:32", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Schoppik-David", "name": { "family": "Schoppik", "given": "David" }, "orcid": "0000-0001-7969-9632" }, { "id": "Bianco-Isaac-H", "name": { "family": "Bianco", "given": "Isaac H." } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Douglass-Adam-D", "name": { "family": "Douglass", "given": "Adam D." }, "orcid": "0000-0001-7859-314X" }, { "id": "Robson-Drew-N", "name": { "family": "Robson", "given": "Drew N." }, "orcid": "0000-0002-0150-1515" }, { "id": "Li-Jennifer-M-B", "name": { "family": "Li", "given": "Jennifer M. B." } }, { "id": "Greenwood-Joel-S-F", "name": { "family": "Greenwood", "given": "Joel S. F." }, "orcid": "0000-0003-2426-8004" }, { "id": "Soucy-Edward-R", "name": { "family": "Soucy", "given": "Edward" }, "orcid": "0000-0002-1187-5596" }, { "id": "Engert-Florian", "name": { "family": "Engert", "given": "Florian" }, "orcid": "0000-0001-8169-2990" }, { "id": "Schier-Alexander-F", "name": { "family": "Schier", "given": "Alexander F." } } ] }, "title": "Gaze-stabilizing central vestibular neurons project asymmetrically to extraocular motoneuron pools", "ispublished": "pub", "full_text_status": "public", "keywords": "anatomy; asymmetry; motoneuron; reflex; vestibular; zebrafish", "note": "\u00a9 2017 Schoppik et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.\n\nReceived: 19 June 2017; Revised: 15 September 2017; Accepted: 19 September 2017; Published: 29 September 2017. \n\nD.S. was supported by a Helen Hay Whitney Postdoctoral Fellowship and National Institute on Deafness and Communication Disorders of the National Institutes of Health Awards K99DC012775 and 5R00DC012775. I.H.B. was supported by Wellcome Trust Sir Henry Wellcome Postdoctoral Fellowship. This work was supported by National Institutes of Health Grants 1R01DA030304 and 1RC2NS069407 to F.E. and Grant R01HL109525 to A.F.S. We thank Robert Baker for inspiration and extensive insights; Omi Ma for discussions and help with retro-orbital fills; Ian Woods for help with transgenesis; Bill Harris for generously providing the atoh7th241/th241; Tg(atoh7:gap43-RFP) line; Clemens Riegler for maintaining the Tg(5\u00d7UAS:sypb-GCaMP3) line; Albert Pan for maintaining the Tg(UAS-E1b:Kaede)s1999t line; the Zebrafish International Resource Center for the Et(E1b:Gal4-VP16)s1101t line; Minoru Koyama for insights into focal lesions; Steve Zimmerman, Karen Hurley, and Jessica Miller for fish care; Bernhard Goetze, Doug Richardson, and Casey Kraft for help with microscopy; Dorothy Barr for library services; and Katherine Nagel and the members of the F.E., A.F.S., and D.S. laboratories, particularly David Ehrlich, Marie Greaney (who provided the fish schematic in Fig. 1), Katherine Harmon, Alix Lacoste, Owen Randlett, and Martin Haesemeyer for helpful discussions.\n\nThe authors declare no competing financial interests.\n\nPublished - 11353.full.pdf
Submitted - 151548.full.pdf
", "abstract": "Within reflex circuits, specific anatomical projections allow central neurons to relay sensations to effectors that generate movements. A major challenge is to relate anatomical features of central neural populations, such as asymmetric connectivity, to the computations the populations perform. To address this problem, we mapped the anatomy, modeled the function, and discovered a new behavioral role for a genetically defined population of central vestibular neurons in rhombomeres 5\u20137 of larval zebrafish. First, we found that neurons within this central population project preferentially to motoneurons that move the eyes downward. Concordantly, when the entire population of asymmetrically projecting neurons was stimulated collectively, only downward eye rotations were observed, demonstrating a functional correlate of the anatomical bias. When these neurons are ablated, fish failed to rotate their eyes following either nose-up or nose-down body tilts. This asymmetrically projecting central population thus participates in both upward and downward gaze stabilization. In addition to projecting to motoneurons, central vestibular neurons also receive direct sensory input from peripheral afferents. To infer whether asymmetric projections can facilitate sensory encoding or motor output, we modeled differentially projecting sets of central vestibular neurons. Whereas motor command strength was independent of projection allocation, asymmetric projections enabled more accurate representation of nose-up stimuli. The model shows how asymmetric connectivity could enhance the representation of imbalance during nose-up postures while preserving gaze stabilization performance. Finally, we found that central vestibular neurons were necessary for a vital behavior requiring maintenance of a nose-up posture: swim bladder inflation. These observations suggest that asymmetric connectivity in the vestibular system facilitates representation of ethologically relevant stimuli without compromising reflexive behavior.", "date": "2017-11-22", "date_type": "published", "publication": "Journal of Neuroscience", "volume": "37", "number": "47", "publisher": "Society for Neuroscience", "pagerange": "11353-11365", "id_number": "CaltechAUTHORS:20171009-110032062", "issn": "0270-6474", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171009-110032062", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Helen Hay Whitney Foundation" }, { "agency": "NIH", "grant_number": "K99DC012775" }, { "agency": "NIH", "grant_number": "5R00DC012775" }, { "agency": "Wellcome Trust" }, { "agency": "NIH", "grant_number": "1R01DA030304" }, { "agency": "NIH", "grant_number": "1RC2NS069407" }, { "agency": "NIH", "grant_number": "R01HL109525" } ] }, "doi": "10.1523/JNEUROSCI.1711-17.2017", "pmcid": "PMC5700419", "primary_object": { "basename": "11353.full.pdf", "url": "https://authors.library.caltech.edu/records/0e1n9-pqz42/files/11353.full.pdf" }, "related_objects": [ { "basename": "151548.full.pdf", "url": "https://authors.library.caltech.edu/records/0e1n9-pqz42/files/151548.full.pdf" } ], "resource_type": "article", "pub_year": "2017", "author_list": "Schoppik, David; Bianco, Isaac H.; et el." }, { "id": "https://authors.library.caltech.edu/records/xe8tq-epk31", "eprint_id": 83139, "eprint_status": "archive", "datestamp": "2023-08-19 05:58:02", "lastmod": "2023-10-17 22:55:33", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lee-Daniel-A", "name": { "family": "Lee", "given": "Daniel A." }, "orcid": "0000-0001-7411-2740" }, { "id": "Andreev-A", "name": { "family": "Andreev", "given": "Andrey" }, "orcid": "0000-0002-7833-1390" }, { "id": "Truong-Thai-V", "name": { "family": "Truong", "given": "Thai V." } }, { "id": "Chen-Audrey", "name": { "family": "Chen", "given": "Audrey" }, "orcid": "0000-0003-2139-9535" }, { "id": "Hill-A-J", "name": { "family": "Hill", "given": "Andrew J." } }, { "id": "Oikonomou-G", "name": { "family": "Oikonomou", "given": "Grigorios" }, "orcid": "0000-0001-6797-7375" }, { "id": "Pham-Uyen", "name": { "family": "Pham", "given": "Uyen" } }, { "id": "Hong-Young-K", "name": { "family": "Hong", "given": "Young K" } }, { "id": "Tran-Steven", "name": { "family": "Tran", "given": "Steven" }, "orcid": "0000-0001-8515-8250" }, { "id": "Glass-Laura", "name": { "family": "Glass", "given": "Laura" } }, { "id": "Sapin-V", "name": { "family": "Sapin", "given": "Viveca" } }, { "id": "Engle-Jae", "name": { "family": "Engle", "given": "Jae" } }, { "id": "Fraser-S-E", "name": { "family": "Fraser", "given": "Scott E." }, "orcid": "0000-0002-5377-0223" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Genetic and neuronal regulation of sleep by neuropeptide VF", "ispublished": "pub", "full_text_status": "public", "keywords": "Sleep, behavior, hypothalamus, neuropeptide VF, NPVF, RFRP, RFamide, neuropeptide, locomotor activity, arousal, genetics", "note": "\u00a9 2017 Lee et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited. \n\nReceived: February 3, 2017; Accepted: November 3, 2017; Accepted Manuscript published: November 6, 2017 (version 1). \n\nWe thank members of the Prober Lab, Paul Sternberg, Elly Chow, Ravi Nath and Han Wang for discussions, and Jason Rihel, Seth Blackshaw and Chanpreet Singh for manuscript comments, as well as Daisy Chilin, Tasha Cammidge, and Hannah Hurley for technical assistance. This work was supported by grants from the NIH (DAL: K99NS097683, F32NS084769; GO: F32NS082010; SEF: MH107238; DAP: NS070911, NS101158, NS095824 and NS101665); the Moore Foundation (SEF); and the Mallinckrodt (DAP), Rita Allen (DAP) and Brain and Behavior Research Foundations (DAP, DAL). We declare no competing interests .\n\nThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.\n\nEthics: Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments were performed using standard protocols (Westerfield, 1993) in accordance with the California Institute of Technology and University of Southern California Institutional Animal Care and Use Committee guidelines.\n\nPublished - elife-25727-v2.pdf
Supplemental Material - elife-25727-supp-v1.zip
", "abstract": "Sleep is an essential and phylogenetically conserved behavioral state, but it remains unclear to what extent genes identified in invertebrates also regulate vertebrate sleep. RFamide-related neuropeptides have been shown to promote invertebrate sleep, and here we report that the vertebrate hypothalamic RFamide neuropeptide VF (NPVF) regulates sleep in the zebrafish, a diurnal vertebrate. We found that NPVF signaling and npvf-expressing neurons are both necessary and sufficient to promote sleep, that mature peptides derived from the NPVF preproprotein promote sleep in a synergistic manner, and that stimulation of npvf-expressing neurons induces neuronal activity levels consistent with normal sleep. These results identify NPVF signaling and npvf-expressing neurons as a novel vertebrate sleep-promoting system and suggest that RFamide neuropeptides participate in an ancient and central aspect of sleep control.", "date": "2017-11-06", "date_type": "published", "publication": "eLife", "volume": "6", "publisher": "eLife Sciences Publications", "pagerange": "Art. No. e25727", "id_number": "CaltechAUTHORS:20171113-083059260", "issn": "2050-084X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171113-083059260", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32NS084769" }, { "agency": "NIH", "grant_number": "NS070911" }, { "agency": "NIH", "grant_number": "DA031367" }, { "agency": "Brain and Behavior Research Foundation", "grant_number": "25392" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Edward Mallinckrodt, Jr. Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Brain and Behavior Research Foundation" }, { "agency": "NIH", "grant_number": "K99NS097683" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32NS082010" }, { "agency": "NIH", "grant_number": "MH107238" }, { "agency": "NIH", "grant_number": "NS060996" } ] }, "doi": "10.7554/eLife.25727", "pmcid": "PMC5705210", "primary_object": { "basename": "elife-25727-supp-v1.zip", "url": "https://authors.library.caltech.edu/records/xe8tq-epk31/files/elife-25727-supp-v1.zip" }, "related_objects": [ { "basename": "elife-25727-v2.pdf", "url": "https://authors.library.caltech.edu/records/xe8tq-epk31/files/elife-25727-v2.pdf" } ], "resource_type": "article", "pub_year": "2017", "author_list": "Lee, Daniel A.; Andreev, Andrey; et el." }, { "id": "https://authors.library.caltech.edu/records/psp7j-nmv35", "eprint_id": 81662, "eprint_status": "archive", "datestamp": "2023-08-21 21:57:37", "lastmod": "2023-10-17 20:56:24", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Nath-Ravi-D", "name": { "family": "Nath", "given": "Ravi D." } }, { "id": "Bedbrook-Claire-N", "name": { "family": "Bedbrook", "given": "Claire N." }, "orcid": "0000-0003-3973-598X" }, { "id": "Abrams-Michael-J", "name": { "family": "Abrams", "given": "Michael J." }, "orcid": "0000-0003-1864-1706" }, { "id": "Basinger-Ty", "name": { "family": "Basinger", "given": "Ty" } }, { "id": "Bois-J-S", "name": { "family": "Bois", "given": "Justin S." }, "orcid": "0000-0001-7137-8746" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173" }, { "id": "Gradinaru-V", "name": { "family": "Gradinaru", "given": "Viviana" }, "orcid": "0000-0001-5868-348X" }, { "id": "Goentoro-L-A", "name": { "family": "Goentoro", "given": "Lea" }, "orcid": "0000-0002-3904-0195" } ] }, "title": "The Jellyfish Cassiopea Exhibits a Sleep-like State", "ispublished": "pub", "full_text_status": "public", "keywords": "evolution of sleep; sleep; Cnidaria; jellyfish; Cassiopea", "note": "\u00a9 2017 Elsevier. \n\nReceived 30 April 2017, Revised 17 July 2017, Accepted 4 August 2017, Available online 21 September 2017. Published: September 21, 2017. \n\nWe thank Chris Blair from the National Aquarium, MD; Monica Medina and Aki Ohdera from Pennsylvania State University, PA; and Wyatt Patry from the Monterey Bay Aquarium, CA, for generously supplying Cassiopea medusa and polyps and Dr. John Bedbrook for critical reading of the manuscript. We thank Kiersten Darrow and Michael Schaadt of the Cabrillo Marine Aquarium, CA, for input on husbandry. We thank http://dryades.units.it/jelly for an image of Cassiopea (CC 3.01 NC-BY-SA) that was adapted in Figure 3 and Figure S1. This work was supported by the NIH Director's New Innovator Award/PECASE (IDP20D017782-01; to V.G.), the James S. McDonnell Foundation for Complex Systems Science (220020365; to L.G.), the NIMH under a Ruth L. Kirschstein National Research Service Award (F31MH102913; to C.N.B.), the NINDS under a Ruth L. Kirschstein National Research Service Award (F31NS100519; to R.D.N.), a National Science Foundation Graduate Research Fellowship (1144469; to M.J.A.), and an NIH training grant (T32GM007616; to C.N.B. and R.D.N.). V.G. is a Heritage Principal Investigator supported by the Heritage Medical Research Institute; P.W.S. is an investigator with the HHMI (047-101), which supported this research. \n\nData and Software Availability: Code used for tracking jellyfish activity and analysis is available at https://github.com/GradinaruLab/Jellyfish. \n\nAuthor Contributions: R.D.N., C.N.B., and M.J.A. conceived the project. V.G., P.W.S., and L.G. oversaw the project. R.D.N., C.N.B., and M.J.A. performed experiments and data analysis. R.D.N., C.N.B., M.J.A., and T.B. conceptualized, designed, and built experimental setups. C.N.B. and R.D.N. wrote image-processing and data-analysis scripts with J.S.B.'s oversight. D.A.P. provided input on experimental design. R.D.N., C.N.B., and M.J.A. wrote the paper with input from J.S.B., D.A.P., V.G., P.W.S., and L.G.\n\nAccepted Version - nihms907190.pdf
Supplemental Material - mmc1.pdf
Supplemental Material - mmc2.mp4
Supplemental Material - mmc3.mp4
Supplemental Material - mmc4.zip
", "abstract": "Do all animals sleep? Sleep has been observed in many vertebrates, and there is a growing body of evidence for sleep-like states in arthropods and nematodes. Here we show that sleep is also present in Cnidaria, an earlier-branching metazoan lineage. Cnidaria and Ctenophora are the first metazoan phyla to evolve tissue-level organization and differentiated cell types, such as neurons and muscle. In Cnidaria, neurons are organized into a non-centralized radially symmetric nerve net that nevertheless shares fundamental properties with the vertebrate nervous system: action potentials, synaptic transmission, neuropeptides, and neurotransmitters . It was reported that cnidarian soft corals and box jellyfish exhibit periods of quiescence, a pre-requisite for sleep-like states, prompting us to ask whether sleep is present in Cnidaria. Within Cnidaria, the upside-down jellyfish Cassiopea spp. displays a quantifiable pulsing behavior, allowing us to perform long-term behavioral tracking. Monitoring of Cassiopea pulsing activity for consecutive days and nights revealed behavioral quiescence at night that is rapidly reversible, as well as a delayed response to stimulation in the quiescent state. When deprived of nighttime quiescence, Cassiopea exhibited decreased activity and reduced responsiveness to a sensory stimulus during the subsequent day, consistent with homeostatic regulation of the quiescent state. Together, these results indicate that Cassiopea has a sleep-like state, supporting the hypothesis that sleep arose early in the metazoan lineage, prior to the emergence of a centralized nervous system.", "date": "2017-10-09", "date_type": "published", "publication": "Current Biology", "volume": "27", "number": "19", "publisher": "Cell Press", "pagerange": "2984-2990", "id_number": "CaltechAUTHORS:20170921-075913502", "issn": "0960-9822", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170921-075913502", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "IDP20D017782-01" }, { "agency": "James S. McDonnell Foundation", "grant_number": "220020365" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "F31MH102913" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "F31NS100519" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1144469" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "T32GM007616" }, { "agency": "Heritage Medical Research Institute" }, { "agency": "Howard Hughes Medical Institute (HHMI)", "grant_number": "047-101" } ] }, "local_group": { "items": [ { "id": "Heritage-Medical-Research-Institute" }, { "id": "Tianqiao-and-Chrissy-Chen-Institute-for-Neuroscience" } ] }, "doi": "10.1016/j.cub.2017.08.014", "pmcid": "PMC5653286", "primary_object": { "basename": "nihms907190.pdf", "url": "https://authors.library.caltech.edu/records/psp7j-nmv35/files/nihms907190.pdf" }, "related_objects": [ { "basename": "mmc1.pdf", "url": "https://authors.library.caltech.edu/records/psp7j-nmv35/files/mmc1.pdf" }, { "basename": "mmc2.mp4", "url": "https://authors.library.caltech.edu/records/psp7j-nmv35/files/mmc2.mp4" }, { "basename": "mmc3.mp4", "url": "https://authors.library.caltech.edu/records/psp7j-nmv35/files/mmc3.mp4" }, { "basename": "mmc4.zip", "url": "https://authors.library.caltech.edu/records/psp7j-nmv35/files/mmc4.zip" } ], "resource_type": "article", "pub_year": "2017", "author_list": "Nath, Ravi D.; Bedbrook, Claire N.; et el." }, { "id": "https://authors.library.caltech.edu/records/j3w9p-mpa87", "eprint_id": 78520, "eprint_status": "archive", "datestamp": "2023-08-21 21:24:33", "lastmod": "2023-10-26 00:10:18", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chen-Shijia", "name": { "family": "Chen", "given": "Shijia" } }, { "id": "Reichert-Sabine", "name": { "family": "Reichert", "given": "Sabine" } }, { "id": "Singh-Chanpreet", "name": { "family": "Singh", "given": "Chanpreet" }, "orcid": "0000-0002-2697-3033" }, { "id": "Oikonomou-Grigorios", "name": { "family": "Oikonomou", "given": "Grigorios" }, "orcid": "0000-0001-6797-7375" }, { "id": "Rihel-Jason", "name": { "family": "Rihel", "given": "Jason" }, "orcid": "0000-0003-4067-2066" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Light-Dependent Regulation of Sleep and Wake States by Prokineticin 2 in Zebrafish", "ispublished": "pub", "full_text_status": "public", "keywords": "prokineticin 2; galanin; sleep; circadian rhythm; masking; zebrafish", "note": "\u00a9 2017 Elsevier B.V. \n\nReceived 25 January 2017, Revised 24 April 2017, Accepted 31 May 2017, Available online 22 June 2017. \n\nWe thank Daisy Chilin, Alex Mack Cruz, and Kenna Molinder for animal husbandry, Viveca Sapin, Brett Niles, and Jae Chu for genotyping and Catherine Oikonomou and members of the Prober lab for comments on the manuscript. This work was supported by grants from the NIH (S.C.: NS077842; D.A.P.: NS070911, NS094390, and NS095824), the Mallinckrodt, Rita Allen and Brain and Behavior Research Foundations (D.A.P.), a Sir Henry Wellcome Trust Fellowship (S.R.), a UCL Excellence Fellowship (J.R.), and a European Research Council Starting Grant (J.R.: 282027).\n\nAccepted Version - nihms882461.pdf
Supplemental Material - mmc1.pdf
", "abstract": "Light affects sleep and wake behaviors by providing an indirect cue that entrains circadian rhythms and also by inducing a direct and rapid regulation of behavior. While circadian entrainment by light is well characterized at the molecular level, mechanisms that underlie the direct effect of light on behavior are largely unknown. In zebrafish, a diurnal vertebrate, we found that both overexpression and mutation of the neuropeptide prokineticin 2 (Prok2) affect sleep and wake behaviors in a light-dependent but circadian-independent manner. In light, Prok2 overexpression increases sleep and induces expression of galanin (galn), a hypothalamic sleep-inducing peptide. We also found that light-dependent, Prok2-induced sedation requires prokineticin receptor 2 (prokr2) and is strongly suppressed in galn mutants. These results suggest that Prok2 antagonizes the direct wake-promoting effect of light in zebrafish, in part through the induction of galn expression in the hypothalamus.", "date": "2017-07-05", "date_type": "published", "publication": "Neuron", "volume": "95", "number": "1", "publisher": "Cell Press", "pagerange": "153-168", "id_number": "CaltechAUTHORS:20170623-125222628", "issn": "0896-6273", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170623-125222628", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "NS077842" }, { "agency": "NIH", "grant_number": "NS070911" }, { "agency": "NIH", "grant_number": "NS094390" }, { "agency": "NIH", "grant_number": "NS095824" }, { "agency": "Mallinckrodt Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Brain and Behavior Research Foundation" }, { "agency": "Wellcome Trust" }, { "agency": "University College London" }, { "agency": "European Research Council (ERC)", "grant_number": "282027" } ] }, "local_group": { "items": [ { "id": "Tianqiao-and-Chrissy-Chen-Institute-for-Neuroscience" } ] }, "doi": "10.1016/j.neuron.2017.06.001", "pmcid": "PMC5653285", "primary_object": { "basename": "mmc1.pdf", "url": "https://authors.library.caltech.edu/records/j3w9p-mpa87/files/mmc1.pdf" }, "related_objects": [ { "basename": "nihms882461.pdf", "url": "https://authors.library.caltech.edu/records/j3w9p-mpa87/files/nihms882461.pdf" } ], "resource_type": "article", "pub_year": "2017", "author_list": "Chen, Shijia; Reichert, Sabine; et el." }, { "id": "https://authors.library.caltech.edu/records/bn0pt-9aq07", "eprint_id": 76469, "eprint_status": "archive", "datestamp": "2023-08-19 03:17:08", "lastmod": "2023-10-25 16:01:44", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Oikonomou-Grigorios", "name": { "family": "Oikonomou", "given": "Grigorios" }, "orcid": "0000-0001-6797-7375" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Attacking sleep from a new angle: contributions from zebrafish", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 Elsevier Ltd. \n\nAvailable online 6 April 2017. \n\nWe thank Catherine Oikonomou, Daniel Lee and Chanpreet Singh for comments on the manuscript. This work was supported by grants from the National Institutes of Health (NS070911, NS094390 and NS095824), the Mallinckrodt Foundation, the Rita Allen Foundation, and the Brain and Behavior Research Foundation to D.A.P., and from the National Institutes of Health (NS082010) and the Della Martin Foundation to G.O.\n\nAccepted Version - nihms866577.pdf
", "abstract": "Sleep consumes a third of our lifespan, but we are far from understanding how it is initiated, maintained and terminated, or what purposes it serves. To address these questions, alternative model systems have recently been recruited. The diurnal zebrafish holds the promise of bridging the gap between simple invertebrate systems, which show little neuroanatomical conservation with mammals, and well-established, but complex and nocturnal, murine systems. Zebrafish larvae can be monitored in a high-throughput fashion, pharmacologically tested by adding compounds into the water, genetically screened using transient transgenesis, and optogenetically manipulated in a non-invasive manner. Here we discuss work that has established the zebrafish as a powerful system for the study of sleep, as well as novel insights gained by exploiting its particular advantages.", "date": "2017-06", "date_type": "published", "publication": "Current Opinion in Neurobiology", "volume": "44", "publisher": "Elsevier", "pagerange": "80-88", "id_number": "CaltechAUTHORS:20170410-104149609", "issn": "0959-4388", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170410-104149609", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "NS070911" }, { "agency": "NIH", "grant_number": "NS094390" }, { "agency": "NIH", "grant_number": "NS095824" }, { "agency": "Mallinckrodt Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Brain and Behavior Research Foundation" }, { "agency": "NIH", "grant_number": "NS082010" }, { "agency": "Della Martin Foundation" } ] }, "doi": "10.1016/j.conb.2017.03.009", "pmcid": "PMC5659277", "primary_object": { "basename": "nihms866577.pdf", "url": "https://authors.library.caltech.edu/records/bn0pt-9aq07/files/nihms866577.pdf" }, "resource_type": "article", "pub_year": "2017", "author_list": "Oikonomou, Grigorios and Prober, David A." }, { "id": "https://authors.library.caltech.edu/records/vjszc-fan68", "eprint_id": 82306, "eprint_status": "archive", "datestamp": "2023-08-19 02:31:30", "lastmod": "2023-10-17 22:10:56", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Suarez-Bregua-P", "name": { "family": "Suarez-Bregua", "given": "P." } }, { "id": "Torres-Nunez-E", "name": { "family": "Torres-Nunez", "given": "E." } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "D." }, "orcid": "0000-0002-7371-4675" }, { "id": "Cerda-Reverter-J-M", "name": { "family": "Cerda-Reverter", "given": "J. M." } }, { "id": "Guerreiro-P-M", "name": { "family": "Guerreiro", "given": "P. M." } }, { "id": "Du-S-J", "name": { "family": "Du", "given": "S. J." } }, { "id": "Canestro-C", "name": { "family": "Canestro", "given": "C." } }, { "id": "Rotllant-J", "name": { "family": "Rotllant", "given": "J." } } ] }, "title": "Genetic and Molecular Analysis of Phosphorus Homeostasis Regulatory Genes. A Key Nutrient for Aquaculture Sustainability", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 Published by Elsevier B.V. \n\nReceived 17 March 2017, Available online 24 March 2017.", "abstract": "[no abstract]", "date": "2017-04-01", "date_type": "published", "publication": "Aquaculture", "volume": "472", "number": "S1", "publisher": "Elsevier", "pagerange": "154", "id_number": "CaltechAUTHORS:20171012-101848464", "issn": "0044-8486", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171012-101848464", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministerio de Ciencia e Innovaci\u00f3n (MCINN)", "grant_number": "ALG2011-23581" }, { "agency": "Campus Do Mar-Xunta de Galicia" } ] }, "doi": "10.1016/j.aquaculture.2017.03.032", "resource_type": "article", "pub_year": "2017", "author_list": "Suarez-Bregua, P.; Torres-Nunez, E.; et el." }, { "id": "https://authors.library.caltech.edu/records/1eymx-4xn31", "eprint_id": 75059, "eprint_status": "archive", "datestamp": "2023-08-22 19:26:26", "lastmod": "2023-10-25 14:42:35", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chen-Audrey", "name": { "family": "Chen", "given": "Audrey" }, "orcid": "0000-0003-2139-9535" }, { "id": "Singh-Chanpreet", "name": { "family": "Singh", "given": "Chanpreet" }, "orcid": "0000-0002-2697-3033" }, { "id": "Oikonomou-Grigorios", "name": { "family": "Oikonomou", "given": "Grigorios" }, "orcid": "0000-0001-6797-7375" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Genetic Analysis of Histamine Signaling in Larval Zebrafish Sleep", "ispublished": "pub", "full_text_status": "public", "keywords": "genetics; histamine; hypocretin; sleep; wake", "note": "Copyright \u00a9 2017 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. \n\nReceived September 22, 2016; accepted February 9, 2017; First published February 15, 2017. \n\nThis work was supported by National Institutes of Health Grants NS060996, NS070911, DA031367, and NS094390; the Mallinckrodt Foundation; the Rita Allen Foundation; and the Brain and Behavior Research Foundation. \n\nAuthor contributions: A.C., C.S., and D.A.P. designed research; A.C., C.S., and D.A.P. performed research; A.C., C.S., and G.O. analyzed data; A.C. and D.A.P. wrote the paper. \n\nThe authors declare no competing financial interests.\n\nPublished - ENEURO.0286-16.2017.full.pdf
", "abstract": "Pharmacological studies in mammals and zebrafish suggest that histamine plays an important role in promoting arousal. However, genetic studies using rodents with disrupted histamine synthesis or signaling have revealed only subtle or no sleep/wake phenotypes. Studies of histamine function in mammalian arousal are complicated by its production in cells of the immune system and its roles in humoral and cellular immunity, which can have profound effects on sleep/wake states. To avoid this potential confound, we used genetics to explore the role of histamine in regulating sleep in zebrafish, a diurnal vertebrate in which histamine production is restricted to neurons in the brain. Similar to rodent genetic studies, we found that zebrafish that lack histamine due to mutation of histidine decarboxylase (hdc) exhibit largely normal sleep/wake behaviors. Zebrafish containing predicted null mutations in several histamine receptors also lack robust sleep/wake phenotypes, although we are unable to verify that these mutants are completely nonfunctional. Consistent with some rodent studies, we found that arousal induced by overexpression of the neuropeptide hypocretin (Hcrt) or by stimulation of hcrt-expressing neurons is not blocked in hdc or hrh1 mutants. We also found that the number of hcrt-expressing or histaminergic neurons is unaffected in animals that lack histamine or Hcrt signaling, respectively. Thus, while acute pharmacological manipulation of histamine signaling has been shown to have profound effects on zebrafish and mammalian sleep, our results suggest that chronic loss of histamine signaling due to genetic mutations has only subtle effects on sleep in zebrafish, similar to rodents.", "date": "2017-01", "date_type": "published", "publication": "eNeuro", "volume": "4", "number": "1", "publisher": "Society for Neuroscience", "pagerange": "Art. No. e0286-16.2017", "id_number": "CaltechAUTHORS:20170313-124518512", "issn": "2373-2822", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170313-124518512", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "NS060996" }, { "agency": "NIH", "grant_number": "NS070911" }, { "agency": "NIH", "grant_number": "DA031367" }, { "agency": "NIH", "grant_number": "NS094390" }, { "agency": "Edward Mallinckrodt, Jr. Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Brain and Behavior Research Foundation" } ] }, "doi": "10.1523/ENEURO.0286-16.2017", "pmcid": "PMC5334454", "primary_object": { "basename": "ENEURO.0286-16.2017.full.pdf", "url": "https://authors.library.caltech.edu/records/1eymx-4xn31/files/ENEURO.0286-16.2017.full.pdf" }, "resource_type": "article", "pub_year": "2017", "author_list": "Chen, Audrey; Singh, Chanpreet; et el." }, { "id": "https://authors.library.caltech.edu/records/4769k-9ap87", "eprint_id": 74058, "eprint_status": "archive", "datestamp": "2023-08-20 14:16:02", "lastmod": "2023-10-24 22:03:07", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Suarez-Bregua-P", "name": { "family": "Suarez-Bregua", "given": "Paula" } }, { "id": "Torres-Nu\u00f1ez-E", "name": { "family": "Torres-Nu\u00f1ez", "given": "Eva" } }, { "id": "Saxena-Ankur", "name": { "family": "Saxena", "given": "Ankur" }, "orcid": "0000-0001-8646-2887" }, { "id": "Guerreiro-P", "name": { "family": "Guerreiro", "given": "Pedro" } }, { "id": "Braasch-I", "name": { "family": "Braasch", "given": "Ingo" }, "orcid": "0000-0003-4766-611X" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Moran-P", "name": { "family": "Moran", "given": "Paloma" }, "orcid": "0000-0002-3644-8507" }, { "id": "Cerda-Reverter-J-M", "name": { "family": "Cerda-Reverter", "given": "Jose Miguel" } }, { "id": "Du-Shao-Jun", "name": { "family": "Du", "given": "Shao Jun" } }, { "id": "Adrio-F", "name": { "family": "Adrio", "given": "Fatima" } }, { "id": "Power-D-M", "name": { "family": "Power", "given": "Deborah M." } }, { "id": "Canario-A-V-M", "name": { "family": "Canario", "given": "Adelino V. M." } }, { "id": "Postlethwait-J-H", "name": { "family": "Postlethwait", "given": "John H." } }, { "id": "Bronner-M-E", "name": { "family": "Bronner", "given": "Marianne E." }, "orcid": "0000-0003-4274-1862" }, { "id": "Ca\u00f1estro-C", "name": { "family": "Ca\u00f1estro", "given": "Cristian" } }, { "id": "Rotllant-J", "name": { "family": "Rotllant", "given": "Josep" } } ] }, "title": "Pth4, an ancient parathyroid hormone lost in eutherian mammals, reveals a new brain-to-bone signaling pathway", "ispublished": "pub", "full_text_status": "public", "keywords": "runx \u2022 phosphate \u2022 calcium \u2022 hypothalamus \u2022 fgf23", "note": "\u00a9 2017 FASEB. \n\nReceived July 27, 2016. Accepted October 11, 2016. Published online before print October 24, 2016. \n\nThe authors thank Yi-lin Yan (University of Oregon) for providing the tip39 (PTH2) expression vector; Prof. N. Lawson (University of Massachusetts Medical School, Worcester, MA, USA) and Prof. K. Kawakami (National Institute of Genetics, Mishima, Japan) for providing the iTol2 constructs; D.A.P. for the hcrt:tdTomato line and Prof. K. M. Kwan (University Of Utah, Salt Lake City, UT, USA) for the bactin2:H2A-mCherry line; In\u00e9s Pazos and Jes\u00fas M\u00e9ndez [Scientific and Technological Research Assistance Centre (CACTI), University of Vigo] for their advice and assistance with the confocal microscope; Rub\u00b4en Chamorro and Rosa Ceinos (IIM\u2013CSIC) for their help in handling and care of the fish and David Guede and Jos\u00e9 R. Caeiro (University of Santiago de Compostela, Santiago, Spain)\nfor their advice and assistance with the micro-CT SkyScan. This\nwork was funded by the Spanish Economy and Competitiveness\nMinistry Project ALG2011-23581 and AGL2014-52473R (to J.R.);\nthe Portuguese Foundation for Science and Technology (Project\nPTDC/BIA-ANM/4225/2012-phos-fate; to P.G.); U. S. National\nInstitutes of Health/Office of the Director Grant R01OD011116\n(alias R01 RR020833; to J.H.P.); Generalitat de Catalunya (Grant\nSGR2014-290) and the Spanish Economy and Competitiveness\nMinistry (Project BFU2010-14875; to C.C.). Partial funding was obtained from Science and Innovation Ministry (AGL2010-22247-C03-01; to J.M.C.-R.), a Campus do Mar Ph.D. grant, and Xunta de Galicia (Santiago, Spain; Project AGL2014-52473R) (to P.S.B.). \n\nJ. Rotllant and P. Suarez-Bregua conceived, designed, and coordinated the study; C. Ca\u00f1estro, I. Braasch, and J. H. Postlethwait performed comparative genomics analyses; P. Suarez-Bregua and E. Torres-Nu\u00f1ez performed promoter and mutation analysis; J. Rotllant performed transgenic lines creation and screening with support from P. Suarez-Bregua and E. Torres-Nu\u00f1ez; J. Cerda-Reverter and P. Suarez-Bregua performed receptor binding studies; P. Suarez-Bregua, A. Saxena, and M. E. Bronner performed laser ablation studies; P. Moran, D. A. Prober, P. Guerreiro,D. M. Power, S. J.Du, F. Adrio, D. M. Power, and A. V. M. Canario provided technical support and contributed to methodology; and P. Suarez-Bregua,\nC. Ca\u00f1estro, and J. Rotllant wrote and revised the manuscript with input from A. Saxena, J. H. Postlethwait, and M. E. Bronner.\n\nSupplemental Material - Supplemental_Figure.docx
Supplemental Material - Supplemental_Figures1.docx
Supplemental Material - Supplemental_Figures2.docx
Supplemental Material - Supplemental_Tables1.docx
", "abstract": "Regulation of bone development, growth, and remodeling traditionally has been thought to depend on endocrine and autocrine/paracrine modulators. Recently, however, brain-derived signals have emerged as key regulators of bone metabolism, although their mechanisms of action have been poorly understood. We reveal the existence of an ancient parathyroid hormone (Pth)4 in zebrafish that was secondarily lost in the eutherian mammals' lineage, including humans, and that is specifically expressed in neurons of the hypothalamus and appears to be a central neural regulator of bone development and mineral homeostasis. Transgenic fish lines enabled mapping of axonal projections leading from the hypothalamus to the brainstem and spinal cord. Targeted laser ablation demonstrated an essential role for of pth4-expressing neurons in larval bone mineralization. Moreover, we show that Runx2 is a direct regulator of pth4 expression and that Pth4 can activate cAMP signaling mediated by Pth receptors. Finally, gain-of-function experiments show that Pth4 can alter calcium/phosphorus levels and affect expression of genes involved in phosphate homeostasis. Based on our discovery and characterization of Pth4, we propose a model for evolution of bone homeostasis in the context of the vertebrate transition from an aquatic to a terrestrial lifestyle.", "date": "2016-10-24", "date_type": "published", "publication": "FASEB Journal", "volume": "31", "number": "2", "publisher": "Federation of American Societies for Experimental Biology", "pagerange": "569-583", "id_number": "CaltechAUTHORS:20170206-080130616", "issn": "0892-6638", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170206-080130616", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministerio de Econom\u00eda y Competitividad (MINECO)", "grant_number": "ALG2011-23581" }, { "agency": "Ministerio de Econom\u00eda y Competitividad (MINECO)", "grant_number": "AGL2014-52473R" }, { "agency": "Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)", "grant_number": "PTDC/BIA-ANM/4225/2012-phos-fate" }, { "agency": "NIH", "grant_number": "R01OD011116" }, { "agency": "NIH", "grant_number": "R01 RR020833" }, { "agency": "Generalitat de Catalunya", "grant_number": "SGR2014-290" }, { "agency": "Ministerio de Econom\u00eda y Competitividad (MINECO)", "grant_number": "BFU2010-14875" }, { "agency": "Ministerio de Econom\u00eda y Competitividad (MINECO)", "grant_number": "AGL2010-22247- C03-01" }, { "agency": "Campus do Mar" }, { "agency": "Xunta de Galicia", "grant_number": "AGL2014-52473R" } ] }, "doi": "10.1096/fj.201600815R", "pmcid": "PMC5240660", "primary_object": { "basename": "Supplemental_Figure.docx", "url": "https://authors.library.caltech.edu/records/4769k-9ap87/files/Supplemental_Figure.docx" }, "related_objects": [ { "basename": "Supplemental_Figures1.docx", "url": "https://authors.library.caltech.edu/records/4769k-9ap87/files/Supplemental_Figures1.docx" }, { "basename": "Supplemental_Figures2.docx", "url": "https://authors.library.caltech.edu/records/4769k-9ap87/files/Supplemental_Figures2.docx" }, { "basename": "Supplemental_Tables1.docx", "url": "https://authors.library.caltech.edu/records/4769k-9ap87/files/Supplemental_Tables1.docx" } ], "resource_type": "article", "pub_year": "2016", "author_list": "Suarez-Bregua, Paula; Torres-Nu\u00f1ez, Eva; et el." }, { "id": "https://authors.library.caltech.edu/records/z27p8-phb40", "eprint_id": 70986, "eprint_status": "archive", "datestamp": "2023-08-22 18:50:54", "lastmod": "2023-10-23 15:14:35", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Choi-Harry-M-T", "name": { "family": "Choi", "given": "Harry M. T." }, "orcid": "0000-0002-1530-0773" }, { "id": "Calvert-Colby-R", "name": { "family": "Calvert", "given": "Colby R." } }, { "id": "Husain-Naeem", "name": { "family": "Husain", "given": "Naeem" }, "orcid": "0000-0003-4962-7237" }, { "id": "Barsi-Julius-C", "name": { "family": "Barsi", "given": "Julius C." }, "orcid": "0000-0002-5161-6708" }, { "id": "Deverman-Benjamin-E", "name": { "family": "Deverman", "given": "Benjamin E." }, "orcid": "0000-0002-6223-9303" }, { "id": "Hunter-Ryan-C", "name": { "family": "Hunter", "given": "Ryan C." }, "orcid": "0000-0003-3841-1676" }, { "id": "Kato-Mihoko", "name": { "family": "Kato", "given": "Mihoko" }, "orcid": "0000-0003-3827-8879" }, { "id": "Lee-S-Melanie", "name": { "family": "Lee", "given": "S. Melanie" } }, { "id": "Abelin-Anna-C-T", "name": { "family": "Abelin", "given": "Anna C. T." } }, { "id": "Rosenthal-Adam-Z", "name": { "family": "Rosenthal", "given": "Adam Z." }, "orcid": "0000-0002-6936-3665" }, { "id": "Akbari-Omar-S", "name": { "family": "Akbari", "given": "Omar S." }, "orcid": "0000-0002-6853-9884" }, { "id": "Li-Yuwei", "name": { "family": "Li", "given": "Yuwei" }, "orcid": "0000-0001-7753-4869" }, { "id": "Hay-B-A", "name": { "family": "Hay", "given": "Bruce A." }, "orcid": "0000-0002-5486-0482" }, { "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173" }, { "id": "Patterson-P-H", "name": { "family": "Patterson", "given": "Paul H." } }, { "id": "Davidson-E-H", "name": { "family": "Davidson", "given": "Eric H." } }, { "id": "Mazmanian-S-K", "name": { "family": "Mazmanian", "given": "Sarkis K." }, "orcid": "0000-0003-2713-1513" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Leadbetter-J-R", "name": { "family": "Leadbetter", "given": "Jared R." }, "orcid": "0000-0002-7033-0844" }, { "id": "Newman-D-K", "name": { "family": "Newman", "given": "Dianne K." }, "orcid": "0000-0003-1647-1918" }, { "id": "Readhead-Carol", "name": { "family": "Readhead", "given": "Carol" } }, { "id": "Bronner-M-E", "name": { "family": "Bronner", "given": "Marianne E." }, "orcid": "0000-0003-4274-1862" }, { "id": "Wold-B-J", "name": { "family": "Wold", "given": "Barbara" }, "orcid": "0000-0003-3235-8130" }, { "id": "Fraser-S-E", "name": { "family": "Fraser", "given": "Scott E." }, "orcid": "0000-0002-5377-0223" }, { "id": "Pierce-N-A", "name": { "family": "Pierce", "given": "Niles A." }, "orcid": "0000-0003-2367-4406" } ] }, "title": "Mapping a multiplexed zoo of mRNA expression", "ispublished": "pub", "full_text_status": "public", "keywords": "In situ hybridization, In situ amplification, Hybridization chain reaction (HCR), Multiplexing, Deep sample penetration, High contrast, Subcellular resolution, Bacteria, Whole-mount embryos and larvae, Tissue sections", "note": "\u00a9 2016. Published by The Company of Biologists Ltd. \n\nReceived May 20, 2016. Accepted August 1, 2016.\n\nThis work was funded by the National Institutes of Health (NIH) [5R01EB006192]; the National Science Foundation Molecular Programming Project [NSF-CCF-1317694]; the Gordon and Betty Moore Foundation [GBMF2809]; the Beckman Institute at Caltech (PMTC); the Translational Biomedical Imaging Laboratory at CHLA; the Translational Imaging Center at USC; a Christensen Fellowship at St Catherine's College, University of Oxford; and by the John Simon Guggenheim Memorial Foundation. Deposited in PMC for release after 12 months. \n\nCompeting interests: The authors declare competing financial interests in the form of patents and pending patent applications. \n\nAuthor contributions: Study conceived by N.A.P. in consultation with M.E.B., E.H.D., S.E.F., B.A.H., J.R.L., D.K.N., P.H.P., M.v.d.R., B.W. Experiments designed by H.M.T.C. and N.A.P. Preliminary studies and protocol adaptation performed by S.M.L., R.C.H., A.Z.R., H.M.T.C. (bacteria), C.R.C. (nematode), N.H. (fly), J.C.B., C.R.C. (urchin), H.M.T.C. (zebrafish), T.S.-S., C.R.C. (chicken), A.C.T.A., B.E.D., D.H., H.M.T.C. (mouse), and H.M.T.C., N.H. (human), in consultation with D.K.N., J.R.L. (bacteria), M.K. (nematode), R.L., S.E.F. (chicken), R.L., C.R.C., S.E.F., B.W. (mouse), M.v.d.R. (human), and H.M.T.C., N.A.P. (all organisms). Final protocols optimized and final data collected by H.M.T.C. (bacteria, zebrafish, mouse), C.R.C. (nematode, urchin, chicken) and N.H. (fly, human). Final data analyzed by: S.M.L., S.K.M., R.C.H., D.K.N., A.Z.R., J.R.L. (bacteria), M.K., P.S., C.R.C. (nematode), O.S.A., B.A.H., N.H. (fly), J.C.B., C.R.C. (urchin), D.A.P., S.E.F. (fish), T.S.-S., M.E.B., C.R.C. (chicken), A.C.T.A., B.W., B.E.D., D.H., Y.L., C.R., R.L., S.E.F. (mouse), A.C.M., M.v.d.R., N.H. (human) and H.M.T.C and N.A.P. (all organisms). Paper and supplementary information written by H.M.T.C. and N.A.P. Paper was edited and approved by all coauthors.\n\nPublished - 3632.full.pdf
Supplemental Material - DEV140137supp.pdf
", "abstract": "In situ hybridization methods are used across the biological sciences to map mRNA expression within intact specimens. Multiplexed experiments, in which multiple target mRNAs are mapped in a single sample, are essential for studying regulatory interactions, but remain cumbersome in most model organisms. Programmable in situ amplifiers based on the mechanism of hybridization chain reaction (HCR) overcome this longstanding challenge by operating independently within a sample, enabling multiplexed experiments to be performed with an experimental timeline independent of the number of target mRNAs. To assist biologists working across a broad spectrum of organisms, we demonstrate multiplexed in situ HCR in diverse imaging settings: bacteria, whole-mount nematode larvae, whole-mount fruit fly embryos, whole-mount sea urchin embryos, whole-mount zebrafish larvae, whole-mount chicken embryos, whole-mount mouse embryos and formalin-fixed paraffin-embedded human tissue sections. In addition to straightforward multiplexing, in situ HCR enables deep sample penetration, high contrast and subcellular resolution, providing an incisive tool for the study of interlaced and overlapping expression patterns, with implications for research communities across the biological sciences.", "date": "2016-10-01", "date_type": "published", "publication": "Development", "volume": "143", "number": "19", "publisher": "Company of Biologists", "pagerange": "3632-3637", "id_number": "CaltechAUTHORS:20161011-070233463", "issn": "0950-1991", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20161011-070233463", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "5R01EB006192" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "Gordon and Betty Moore Foundation", "grant_number": "GBMF2809" }, { "agency": "Caltech Beckman Institute" }, { "agency": "CHLA Translational Biomedical Imaging Laboratory" }, { "agency": "USC Translational Imaging Center" }, { "agency": "St. Catharine's College" }, { "agency": "University of Oxford" }, { "agency": "John Simon Guggenheim Memorial Foundation" } ] }, "local_group": { "items": [ { "id": "Division-of-Geological-and-Planetary-Sciences" } ] }, "doi": "10.1242/dev.140137", "pmcid": "PMC5087610", "primary_object": { "basename": "3632.full.pdf", "url": "https://authors.library.caltech.edu/records/z27p8-phb40/files/3632.full.pdf" }, "related_objects": [ { "basename": "DEV140137supp.pdf", "url": "https://authors.library.caltech.edu/records/z27p8-phb40/files/DEV140137supp.pdf" } ], "resource_type": "article", "pub_year": "2016", "author_list": "Choi, Harry M. T.; Calvert, Colby R.; et el." }, { "id": "https://authors.library.caltech.edu/records/teya7-2ff79", "eprint_id": 71213, "eprint_status": "archive", "datestamp": "2023-08-20 14:02:28", "lastmod": "2023-10-23 15:29:50", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhao-Yali", "name": { "family": "Zhao", "given": "Yali" } }, { "id": "Singh-Chanpreet", "name": { "family": "Singh", "given": "Chanpreet" }, "orcid": "0000-0002-2697-3033" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Wayne-Nancy-L", "name": { "family": "Wayne", "given": "Nancy L." }, "orcid": "0000-0003-2784-6308" } ] }, "title": "Morphological and Physiological Interactions Between GnRH3 and Hypocretin/Orexin Neuronal Systems in Zebrafish (Danio rerio)", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2016 Endocrine Society. \n\nReceived: June 02, 2016; Accepted: August 11, 2016; First Published Online: August 17, 2016. \n\nWe thank Ms Yuan Dong for animal care and Dr Meng-Chin Lin and Matthew Farajzadeh for technical assistance. \n\nThis work was supported by grants from the University of California-Los Angeles Office of the Vice Chancellor for Research and the Dean's Office of the David Geffen School of Medicine at University of California-Los Angeles (N.L.W.) and by the National Institutes of Health (D.P.). \n\nThe authors have nothing to disclose.", "abstract": "GnRH neurons integrate internal and external cues to control sexual maturation and fertility. Homeostasis of energy balance and food intake correlates strongly with the status of reproduction. Neuropeptides secreted by the hypothalamus involved in modulating energy balance and feeding may play additional roles in the regulation of reproduction. Hypocretin (Hcrt) (also known as orexin) is one such peptide, primarily controlling sleep/wakefulness, food intake, and reward processing. There is a growing body of evidence indicating that Hcrt/orexin (Hcrt) modulates reproduction through interacting with the hypothalamo-pituitary-gonadal axis in mammals. To explore potential morphological and functional interactions between the GnRH and Hcrt neuronal systems, we employed a variety of experimental approaches including confocal imaging, immunohistochemistry, and electrophysiology in transgenic zebrafish, in which fluorescent proteins are genetically expressed in GnRH3 and Hcrt neurons. Our imaging data revealed close apposition and direct connection between GnRH3 and Hcrt neuronal systems in the hypothalamus during larval development through adulthood. Furthermore, the Hcrt receptor (HcrtR) is expressed in GnRH3 neurons. Electrophysiological data revealed a reversible inhibitory effect of Hcrt on GnRH3 neuron electrical activity, which was blocked by the HcrtR antagonist almorexant. In addition, Hcrt had no effect on the electrical activity of GnRH3 neurons in the HcrtR null mutant zebrafish (HcrtR\u2212/\u2212). Our findings demonstrate a close anatomical and functional relationship between Hcrt and GnRH neuronal systems in zebrafish. It is the first demonstration of a link between neuronal circuits controlling sleeping/arousal/feeding and reproduction in zebrafish, an important animal model for investigating the molecular genetics of development.", "date": "2016-10", "date_type": "published", "publication": "Endocrinology", "volume": "157", "number": "10", "publisher": "Endocrine Society", "pagerange": "4012-4020", "id_number": "CaltechAUTHORS:20161018-095229722", "issn": "0013-7227", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20161018-095229722", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "University of California Los Angeles (UCLA)" }, { "agency": "NIH" } ] }, "doi": "10.1210/en.2016-1381", "pmcid": "PMC5045510", "resource_type": "article", "pub_year": "2016", "author_list": "Zhao, Yali; Singh, Chanpreet; et el." }, { "id": "https://authors.library.caltech.edu/records/9x4vy-xj986", "eprint_id": 64542, "eprint_status": "archive", "datestamp": "2023-08-20 10:24:17", "lastmod": "2023-10-17 21:29:23", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chiu-Cindy-N", "name": { "family": "Chiu", "given": "Cindy N." } }, { "id": "Rihel-Jason", "name": { "family": "Rihel", "given": "Jason" }, "orcid": "0000-0003-4067-2066" }, { "id": "Lee-Daniel-A", "name": { "family": "Lee", "given": "Daniel A." }, "orcid": "0000-0001-7411-2740" }, { "id": "Singh-Chanpreet", "name": { "family": "Singh", "given": "Chanpreet" }, "orcid": "0000-0002-2697-3033" }, { "id": "Mosser-Eric-A", "name": { "family": "Mosser", "given": "Eric A." } }, { "id": "Chen-Shijia", "name": { "family": "Chen", "given": "Shijia" } }, { "id": "Sapin-Viveca", "name": { "family": "Sapin", "given": "Viveca" } }, { "id": "Pham-Uyen", "name": { "family": "Pham", "given": "Uyen" } }, { "id": "Engle-Jae", "name": { "family": "Engle", "given": "Jae" } }, { "id": "Niles-Brett-J", "name": { "family": "Niles", "given": "Brett J." } }, { "id": "Montz-Christin-J", "name": { "family": "Montz", "given": "Christin J." } }, { "id": "Chakravarthy-Sridhara", "name": { "family": "Chakravarthy", "given": "Sridhara" } }, { "id": "Zimmerman-Steven", "name": { "family": "Zimmerman", "given": "Steven" } }, { "id": "Salehi-Ashtiani-Kourosh", "name": { "family": "Salehi-Ashtiani", "given": "Kourosh" }, "orcid": "0000-0002-6521-5243" }, { "id": "Vidal-Marc", "name": { "family": "Vidal", "given": "Marc" }, "orcid": "0000-0003-3391-5410" }, { "id": "Schier-Alexander-F", "name": { "family": "Schier", "given": "Alexander F." }, "orcid": "0000-0002-5317-494X" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2016 Elsevier. \n\nReceived 17 April 2015, Revised 16 November 2015, Accepted 24 December 2015, Available online 17 February 2016. \n\nWe thank Melanie Pribisko, Alex Mack Cruz, Axel Dominguez, Sohini Khan, and Kenna Molinder for technical assistance. This work was supported by grants from the NIH (D.A.L.: NS084769; S. Chen: NS077842; A.F.S.: HL109625; D.A.P.: NS060996, NS070911, DA031367); the European Research Council Starting Grant and UCL Excellence Fellowship (J.R.); the High-Tech Fund of the Dana-Farber Cancer Institute and the Ellison Foundation (M.V.); and the Mallinckrodt, Rita Allen and the Brain and Behavior Research Foundations (D.A.P.). We declare no conflicts of interest. \n\nAuthor Contributions: A.F.S. and D.A.P. conceived the genetic screen. D.A.P. and J.R. designed and performed the experiments for the primary genetic screen. C.N.C., J.R., D.A.L., C.S., E.A.M., S. Chen, V.S., U.P., J.E., B.J.N., C.J.M., S. Chakravarthy, and D.A.P. performed secondary screening of human and zebrafish stable lines. All subsequent work was conceived by, and performed in the lab of, D.A.P., except that adult assays were performed by J.R. using a setup designed and built by S.Z. D.A.P. and C.N.C. generated mutants. C.N.C. designed, performed, and analyzed most Nmu experiments, except that C.S. performed some mutant experiments. K.S.-A. and M.V. provided reagents. C.N.C., J.R., A.F.S., and D.A.P. wrote the manuscript. D.A.P. and A.F.S. supervised the project.\n\nAccepted Version - nihms750662.pdf
Supplemental Material - mmc1.pdf
Supplemental Material - mmc2.mp4
Supplemental Material - mmc3.mp4
", "abstract": "Neuromodulation of arousal states ensures that an animal appropriately responds to its environment and engages in behaviors necessary for survival. However, the molecular and circuit properties underlying neuromodulation of arousal states such as sleep and wakefulness remain unclear. To tackle this challenge in a systematic and unbiased manner, we performed a genetic overexpression screen to identify genes that affect larval zebrafish arousal. We found that the neuropeptide neuromedin U (Nmu) promotes hyperactivity and inhibits sleep in zebrafish larvae, whereas nmu mutant animals are hypoactive. We show that Nmu-induced arousal requires Nmu receptor 2 and signaling via corticotropin releasing hormone (Crh) receptor 1. In contrast to previously proposed models, we find that Nmu does not promote arousal via the hypothalamic-pituitary-adrenal axis, but rather probably acts via brainstem crh-expressing neurons. These results reveal an unexpected functional and anatomical interface between the Nmu system and brainstem arousal systems that represents a novel wake-promoting pathway.", "date": "2016-02-17", "date_type": "published", "publication": "Neuron", "volume": "89", "number": "4", "publisher": "Cell Press", "pagerange": "842-856", "id_number": "CaltechAUTHORS:20160218-075222867", "issn": "0896-6273", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160218-075222867", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "NS084769" }, { "agency": "NIH", "grant_number": "NS077842" }, { "agency": "NIH", "grant_number": "HL109625" }, { "agency": "NIH", "grant_number": "NS060996" }, { "agency": "NIH", "grant_number": "NS070911" }, { "agency": "NIH", "grant_number": "DA031367" }, { "agency": "European Research Council (ERC)" }, { "agency": "University College London" }, { "agency": "Dana-Farber Cancer Institute" }, { "agency": "Ellison Foundation" }, { "agency": "Mallinckrodt Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Brain and Behavior Research Foundation" } ] }, "doi": "10.1016/j.neuron.2016.01.007", "pmcid": "PMC4851465", "primary_object": { "basename": "mmc1.pdf", "url": "https://authors.library.caltech.edu/records/9x4vy-xj986/files/mmc1.pdf" }, "related_objects": [ { "basename": "mmc2.mp4", "url": "https://authors.library.caltech.edu/records/9x4vy-xj986/files/mmc2.mp4" }, { "basename": "mmc3.mp4", "url": "https://authors.library.caltech.edu/records/9x4vy-xj986/files/mmc3.mp4" }, { "basename": "nihms750662.pdf", "url": "https://authors.library.caltech.edu/records/9x4vy-xj986/files/nihms750662.pdf" } ], "resource_type": "article", "pub_year": "2016", "author_list": "Chiu, Cindy N.; Rihel, Jason; et el." }, { "id": "https://authors.library.caltech.edu/records/3mtp2-j5q52", "eprint_id": 64496, "eprint_status": "archive", "datestamp": "2023-08-22 17:21:25", "lastmod": "2023-10-23 20:15:36", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chen-Audrey", "name": { "family": "Chen", "given": "Audrey" }, "orcid": "0000-0003-2139-9535" }, { "id": "Chiu-Cindy-N", "name": { "family": "Chiu", "given": "Cindy N." } }, { "id": "Mosser-Eric-A", "name": { "family": "Mosser", "given": "Eric A." } }, { "id": "Kahn-Sohini", "name": { "family": "Kahn", "given": "Sohini" } }, { "id": "Spence-Rory", "name": { "family": "Spence", "given": "Rory" }, "orcid": "0000-0002-1898-0129" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "QRFP and Its Receptors Regulate Locomotor Activity and Sleep in Zebrafish", "ispublished": "pub", "full_text_status": "public", "keywords": "26RFa; Gpr103; P518; QRFP; sleep; zebrafish", "note": "\u00a9 2016 the authors. Beginning six months after publication the Work will be made freely available to the public on SfN's website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/). \n\nReceived July 7, 2015; revised Nov. 13, 2015; accepted Dec. 12, 2015. \n\nThis work was supported by grants from the National Institutes of Health (NS-060996, NS-070911, and DA-031367), the Mallinckrodt Foundation, the Rita Allen Foundation, and the Brain and Behavior Research Foundation to D.A.P. We thank Alex Mack Cruz, Axel Dominguez, and Kenna Molinder for animal husbandry assistance; Viveca Sapin, Brett Niles, and Jae Chu for technical assistance; and Andres Collazo for imaging assistance. \n\nAuthor contributions: A.C., C.N.C., and D.A.P. designed research; A.C., C.N.C., E.A.M., S.K., R.S., and D.A.P. performed research; A.C., C.N.C., E.A.M., and D.A.P. analyzed data; A.C., C.N.C., and D.A.P. wrote the paper.\n\nA.C. and C.N.C. contributed equally to this work.\n\nErratum: Chen et al., QRFP and Its Receptors Regulate Locomotor Activity and Sleep in Zebrafish\nThe Journal of Neuroscience, 11 May 2016, 36(19): 5429-5430; doi: 10.1523/JNEUROSCI.1200-16.2016\n\nPublished - 1823.full.pdf
Erratum - 5429.full.pdf
", "abstract": "The hypothalamus plays an important role in regulating sleep, but few hypothalamic sleep-promoting signaling pathways have been identified. Here we demonstrate a role for the neuropeptide QRFP (also known as P518 and 26RFa) and its receptors in regulating sleep in zebrafish, a diurnal vertebrate. We show that QRFP is expressed in \u223c10 hypothalamic neurons in zebrafish larvae, which project to the hypothalamus, hindbrain, and spinal cord, including regions that express the two zebrafish QRFP receptor paralogs. We find that the overexpression of QRFP inhibits locomotor activity during the day, whereas mutation of qrfp or its receptors results in increased locomotor activity and decreased sleep during the day. Despite the restriction of these phenotypes to the day, the circadian clock does not regulate qrfp expression, and entrained circadian rhythms are not required for QRFP-induced rest. Instead, we find that QRFP overexpression decreases locomotor activity largely in a light-specific manner. Our results suggest that QRFP signaling plays an important role in promoting sleep and may underlie some aspects of hypothalamic sleep control.", "date": "2016-02-10", "date_type": "published", "publication": "Journal of Neuroscience", "volume": "36", "number": "6", "publisher": "Society for Neuroscience", "pagerange": "1823-1840", "id_number": "CaltechAUTHORS:20160216-100016101", "issn": "0270-6474", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160216-100016101", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "NS-060996" }, { "agency": "NIH", "grant_number": "NS-070911" }, { "agency": "NIH", "grant_number": "DA-031367" }, { "agency": "Mallinckrodt Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Brain and Behavior Research Foundation" } ] }, "doi": "10.1523/JNEUROSCI.2579-15.2016", "pmcid": "PMC4748070", "primary_object": { "basename": "1823.full.pdf", "url": "https://authors.library.caltech.edu/records/3mtp2-j5q52/files/1823.full.pdf" }, "related_objects": [ { "basename": "5429.full.pdf", "url": "https://authors.library.caltech.edu/records/3mtp2-j5q52/files/5429.full.pdf" } ], "resource_type": "article", "pub_year": "2016", "author_list": "Chen, Audrey; Chiu, Cindy N.; et el." }, { "id": "https://authors.library.caltech.edu/records/qkreg-5ad57", "eprint_id": 61752, "eprint_status": "archive", "datestamp": "2023-08-20 10:04:08", "lastmod": "2023-10-25 15:42:19", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chen-Shijia", "name": { "family": "Chen", "given": "Shijia" } }, { "id": "Chiu-Cindy-N", "name": { "family": "Chiu", "given": "Cindy N." } }, { "id": "McArthur-K-L", "name": { "family": "McArthur", "given": "Kimberly L." } }, { "id": "Fetcho-J-R", "name": { "family": "Fetcho", "given": "Joseph R." } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "TRP channel mediated neuronal activation and ablation in freely behaving zebrafish", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2015 Nature Publishing Group. \n\nReceived 03 September 2015; Accepted 09 November 2015; Published online 14 December 2015. \n\nWe thank A. Chen, A. Cruz, A. Dominguez, J. Engle, S. Khan, K. Molinder, B. Niles, V. Sapin and L. Wang for technical assistance. This work was supported by grants from the US National Institutes of Health (F31-NS07842A to S.C.; F32-NS083099 to K.L.M.; R01-NS26539 and DP1-OD006411 to J.R.F.; R00-NS060996, R01-NS070911 and R01-DA031367 to D.A.P.) and the Mallinckrodt Foundation, the Rita Allen Foundation and the Brain and Behavior Research Foundation (D.A.P.). \n\nAuthor Contributions: D.A.P. conceived of and supervised the project. S.C. and C.N.C. designed, performed, and analyzed all experiments, except physiology experiments, which were designed, performed and analyzed by K.L.M. and J.R.F. All authors collaborated to write the manuscript. \n\nThe authors declare no competing financial interests.\n\nAccepted Version - nihms739996.pdf
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", "abstract": "The zebrafish (Danio rerio) is a useful vertebrate model system in which to study neural circuits and behavior, but tools to modulate neurons in freely behaving animals are limited. As poikilotherms that live in water, zebrafish are amenable to thermal and pharmacological perturbations. We exploit these properties by using transient receptor potential (TRP) channels to activate or ablate specific neuronal populations using the chemical and thermal agonists of heterologously expressed TRPV1, TRPM8 and TRPA1.", "date": "2016-02", "date_type": "published", "publication": "Nature Methods", "volume": "13", "number": "2", "publisher": "Nature Publishing Group", "pagerange": "147-150", "id_number": "CaltechAUTHORS:20151030-151749046", "issn": "1548-7091", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151030-151749046", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "F31-NS07842A" }, { "agency": "NIH", "grant_number": "F32-NS083099" }, { "agency": "NIH", "grant_number": "R01-NS26539" }, { "agency": "NIH", "grant_number": "DP1-OD006411" }, { "agency": "NIH", "grant_number": "R00-NS060996" }, { "agency": "NIH", "grant_number": "R01-NS070911" }, { "agency": "NIH", "grant_number": "R01-DA031367" }, { "agency": "Mallinckrodt Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Brain and Behavior Research Foundation" } ] }, "doi": "10.1038/nmeth.3691", "pmcid": "PMC4851460", "primary_object": { "basename": "nmeth.3691-SF7.jpg", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-SF7.jpg" }, "related_objects": [ { "basename": "nmeth.3691-SF9.jpg", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-SF9.jpg" }, { "basename": "nmeth.3691-sv2.mp4", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-sv2.mp4" }, { "basename": "nmeth.3691-sv3.mp4", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-sv3.mp4" }, { "basename": "nmeth.3691-SF2.jpg", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-SF2.jpg" }, { "basename": "nmeth.3691-SF4.jpg", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-SF4.jpg" }, { "basename": "nmeth.3691-SF8.jpg", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-SF8.jpg" }, { "basename": "nmeth.3691-S2.zip", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-S2.zip" }, { "basename": "nmeth.3691-SF5.jpg", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-SF5.jpg" }, { "basename": "nmeth.3691-SF6.jpg", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-SF6.jpg" }, { "basename": "nihms739996.pdf", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nihms739996.pdf" }, { "basename": "nmeth.3691-S1.pdf", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-S1.pdf" }, { "basename": "nmeth.3691-SF3.jpg", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-SF3.jpg" }, { "basename": "nmeth.3691-sv1.mp4", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-sv1.mp4" }, { "basename": "nmeth.3691-sv4.mp4", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-sv4.mp4" }, { "basename": "nmeth.3691-SF1.jpg", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-SF1.jpg" }, { "basename": "nmeth.3691-SF10.jpg", "url": "https://authors.library.caltech.edu/records/qkreg-5ad57/files/nmeth.3691-SF10.jpg" } ], "resource_type": "article", "pub_year": "2016", "author_list": "Chen, Shijia; Chiu, Cindy N.; et el." }, { "id": "https://authors.library.caltech.edu/records/62f84-gp794", "eprint_id": 60235, "eprint_status": "archive", "datestamp": "2023-08-20 08:13:04", "lastmod": "2023-10-24 15:28:04", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Singh-C", "name": { "family": "Singh", "given": "Chanpreet" }, "orcid": "0000-0002-2697-3033" }, { "id": "Oikonomou-G", "name": { "family": "Oikonomou", "given": "Grigorios" }, "orcid": "0000-0001-6797-7375" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Norepinephrine is required to promote wakefulness and for hypocretin-induced arousal in zebrafish", "ispublished": "pub", "full_text_status": "public", "keywords": "norepinephrine, noradrenaline, dopamine beta hydroxylase, hypocretin, sleep, zebrafish", "note": "\u00a9 2015 The authors. Copyright Singh et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. \n\nWe thank Mike Walsh for assistance with the optogenetic and tapping assays, Andres Collazo for imaging assistance, Viveca Sapin and Jae Engle for genotyping assistance, and Catherine Oikonomou for critical reading of the manuscript. This work was supported by grants from the NIH (GO: F32NS082010; DAP: NS060996, NS070911 and DA031367), the Mallinckrodt Foundation, the Rita Allen Foundation and the Brain and Behavior Research Foundation (D.A.P.). We declare no competing interests.\n\nPublished - e07000.full.pdf
", "abstract": "Pharmacological studies in mammals suggest that norepinephrine (NE) plays an important role in promoting arousal. However, the role of endogenous NE is unclear, with contradicting reports concerning the sleep phenotypes of mice lacking NE due to mutation of dopamine \u03b2-hydroxylase (dbh). To investigate NE function in an alternative vertebrate model, we generated dbh mutant zebrafish. In contrast to mice, these animals exhibit dramatically increased sleep. Surprisingly, despite an increase in sleep,dbh mutant zebrafish have a reduced arousal threshold. These phenotypes are also observed in zebrafish treated with small molecules that inhibit NE signaling, suggesting that they are caused by the lack of NE. Using genetic overexpression of hypocretin (Hcrt) and optogenetic activation of hcrt-expressing neurons, we also find that NE is important for Hcrt-induced arousal. These results establish a role for endogenous NE in promoting arousal and indicate that NE is a critical downstream effector of Hcrt neurons.", "date": "2015-09-16", "date_type": "published", "publication": "eLife", "volume": "4", "publisher": "eLife Sciences Publications", "pagerange": "Art. No. e07000", "id_number": "CaltechAUTHORS:20150914-202225418", "issn": "2050-084X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150914-202225418", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "F32NS082010" }, { "agency": "NIH", "grant_number": "NS060996" }, { "agency": "NIH", "grant_number": "NS070911" }, { "agency": "NIH", "grant_number": "DA031367" }, { "agency": "Edward Mallinckrodt, Jr. Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Brain and Behavior Research Foundation" } ] }, "doi": "10.7554/eLife.07000", "pmcid": "PMC4606453", "primary_object": { "basename": "e07000.full.pdf", "url": "https://authors.library.caltech.edu/records/62f84-gp794/files/e07000.full.pdf" }, "resource_type": "article", "pub_year": "2015", "author_list": "Singh, Chanpreet; Oikonomou, Grigorios; et el." }, { "id": "https://authors.library.caltech.edu/records/59qy4-6g461", "eprint_id": 55540, "eprint_status": "archive", "datestamp": "2023-08-20 05:27:53", "lastmod": "2023-10-20 22:21:52", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Gandhi-A-V", "name": { "family": "Gandhi", "given": "Avni V." } }, { "id": "Mosser-E-A", "name": { "family": "Mosser", "given": "Eric A." } }, { "id": "Oikonomou-G", "name": { "family": "Oikonomou", "given": "Grigorios" }, "orcid": "0000-0001-6797-7375" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Melatonin Is Required for the Circadian Regulation of Sleep", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2015 Elsevier Inc.\n\nReceived: April 14, 2014; Revised: December 15, 2014; Accepted: January 27, 2015; Published: March 5, 2015.\n\nWe thank Jason Rihel, Kathy Tamai, Michael Rosbash, Daniel Lee, Catherine Oikonomou, and Chanpreet Singh for critical reading of the manuscript and Melanie Pribisko Yen for assistance with melatonin isolation. This work was supported by a Della Martin postdoctoral fellowship (E.M.), NIH grants (G.O.: F32NS082010; D.A.P.: NS060996, NS070911 and DA031367), the Mallinckrodt Foundation, the Rita Allen Foundation, and the Brain and Behavior Research Foundation (D.A.P.).\n\nAuthor Contributions:\nA.V.G. performed all experiments except circadian rhythm and ELISA assays\n(E.A.M.) and arousal threshold assays (G.O.). A.V.G., E.A.M., G.O., and D.A.P.\nanalyzed the data and wrote the manuscript.\n\nSupplemental Material - mmc1.pdf
", "abstract": "Sleep is an evolutionarily conserved behavioral state whose regulation is poorly understood. A classical model posits that sleep is regulated by homeostatic and circadian mechanisms. Several factors have been implicated in mediating the homeostatic regulation of sleep, but molecules underlying the circadian mechanism are unknown. Here we use animals lacking melatonin due to mutation of arylalkylamine N-acetyltransferase 2 (aanat2) to show that melatonin is required for circadian regulation of sleep in zebrafish. Sleep is dramatically reduced at night in aanat2 mutants maintained in light/dark conditions, and the circadian regulation of sleep is abolished in free-running conditions. We find that melatonin promotes sleep downstream of the circadian clock as it is not required to initiate or maintain circadian rhythms. Additionally, we provide evidence that melatonin may induce sleep in part by promoting adenosine signaling, thus potentially linking circadian and homeostatic control of sleep.", "date": "2015-03-18", "date_type": "published", "publication": "Neuron", "volume": "85", "number": "6", "publisher": "Elsevier", "pagerange": "1193-1199", "id_number": "CaltechAUTHORS:20150305-104130791", "issn": "0896-6273", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150305-104130791", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Della Martin Postdoctoral Fellowship" }, { "agency": "NIH", "grant_number": "F32NS082010" }, { "agency": "NIH", "grant_number": "NS060996" }, { "agency": "NIH", "grant_number": "NS070911" }, { "agency": "NIH", "grant_number": "DA031367" }, { "agency": "Mallinckrodt Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Brain and Behavior Research Foundation" } ] }, "doi": "10.1016/j.neuron.2015.02.016", "pmcid": "PMC4851458", "primary_object": { "basename": "mmc1.pdf", "url": "https://authors.library.caltech.edu/records/59qy4-6g461/files/mmc1.pdf" }, "resource_type": "article", "pub_year": "2015", "author_list": "Gandhi, Avni V.; Mosser, Eric A.; et el." }, { "id": "https://authors.library.caltech.edu/records/gsw9a-rkb33", "eprint_id": 55450, "eprint_status": "archive", "datestamp": "2023-08-20 05:25:39", "lastmod": "2023-10-20 22:15:32", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Liu-Justin", "name": { "family": "Liu", "given": "Justin" }, "orcid": "0000-0002-5338-6491" }, { "id": "Merkle-Florian-T", "name": { "family": "Merkle", "given": "Florian T." } }, { "id": "Gandhi-Avni-V", "name": { "family": "Gandhi", "given": "Avni V." } }, { "id": "Gagnon-James-A", "name": { "family": "Gagnon", "given": "James A." } }, { "id": "Woods-Ian-G", "name": { "family": "Woods", "given": "Ian G." } }, { "id": "Chiu-Cindy-N", "name": { "family": "Chiu", "given": "Cindy N." } }, { "id": "Shimogori-Tomomi", "name": { "family": "Shimogori", "given": "Tomomi" } }, { "id": "Schier-Alexander-F", "name": { "family": "Schier", "given": "Alexander F." }, "orcid": "0000-0002-5317-494X" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Evolutionarily conserved regulation of hypocretin neuron specification by Lhx9", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2015 The Company of Biologists Ltd. \n\nReceived September 3, 2014; accepted January 15, 2015. Posted online before print February 27, 2015.\n\nWe thank Farhad Imam for assistance with microarray data analysis, Anthony Kirilushna for EMSA assistance and Daniel Lee for comments on the manuscript. This work was supported by grants from the National Institutes of Health [F31NS77844 to J.L.; 1R21NS071598, 5K99NS083713 to F.T.M.; R01HL109525, R21NS071598 to A.F.S.; R00NS060996, R01NS070911, R01DA031367 to D.A.P.], the American Cancer Society [to J.A.G. and I.G.W.], the Jane Coffin Childs Memorial Fund for Medical Research [to F.T.M.], the RIKEN Brain Institute [to T.S.], the Mallinckrodt Foundation, the Rita Allen Foundation, and the Brain and Behavior Research Foundation [to D.A.P.]. Deposited in PMC for release after 12 months.\n\nPublished - Development-2015-Liu-1113-24.pdf
", "abstract": "Loss of neurons that express the neuropeptide hypocretin (Hcrt) has been implicated in narcolepsy, a debilitating disorder characterized by excessive daytime sleepiness and cataplexy. Cell replacement therapy, using Hcrt-expressing neurons generated in vitro, is a potentially useful therapeutic approach, but factors sufficient to specify Hcrt neurons are unknown. Using zebrafish as a high-throughput system to screen for factors that can specify Hcrt neurons in vivo, we identified the LIM homeobox transcription factor Lhx9 as necessary and sufficient to specify Hcrt neurons. We found that Lhx9 can directly induce hcrt expression and we identified two potential Lhx9 binding sites in the zebrafish hcrt promoter. Akin to its function in zebrafish, we found that Lhx9 is sufficient to specify Hcrt-expressing neurons in the developing mouse hypothalamus. Our results elucidate an evolutionarily conserved role for Lhx9 in Hcrt neuron specification that improves our understanding of Hcrt neuron development.", "date": "2015-03-15", "date_type": "published", "publication": "Development", "volume": "142", "number": "6", "publisher": "Company of Biologists", "pagerange": "1113-1124", "id_number": "CaltechAUTHORS:20150303-083605759", "issn": "0950-1991", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150303-083605759", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F31NS77844" }, { "agency": "NIH", "grant_number": "1R21NS071598" }, { "agency": "NIH", "grant_number": "5K99NS083713" }, { "agency": "NIH", "grant_number": "R01HL109525" }, { "agency": "NIH", "grant_number": "R21NS071598" }, { "agency": "NIH", "grant_number": "R00NS060996" }, { "agency": "NIH", "grant_number": "R01NS070911" }, { "agency": "NIH", "grant_number": "R01DA031367" }, { "agency": "American Cancer Society" }, { "agency": "Jane Coffin Childs Memorial Fund for Medical Research" }, { "agency": "RIKEN Brain Institute" }, { "agency": "Mallinckrodt Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Brain and Behavior Research Foundation" } ] }, "doi": "10.1242/dev.117424", "pmcid": "PMC4360184", "primary_object": { "basename": "Development-2015-Liu-1113-24.pdf", "url": "https://authors.library.caltech.edu/records/gsw9a-rkb33/files/Development-2015-Liu-1113-24.pdf" }, "resource_type": "article", "pub_year": "2015", "author_list": "Liu, Justin; Merkle, Florian T.; et el." }, { "id": "https://authors.library.caltech.edu/records/ms6ta-ykt68", "eprint_id": 38717, "eprint_status": "archive", "datestamp": "2023-08-19 19:32:10", "lastmod": "2023-10-23 23:24:06", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chiu-Cindy-N", "name": { "family": "Chiu", "given": "Cindy N." } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "Regulation of zebrafish sleep and arousal states: current and prospective approaches", "ispublished": "pub", "full_text_status": "public", "keywords": "zebrafish, sleep, arousal, hypocretin, orexin, neuromodulator", "note": "\u00a9 2013 Chiu and Prober. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.\nReceived: 07 February 2013; Paper pending published: 03 March 2013; Accepted: 14 March 2013; Published online: 09 April 2013.\nThis work was supported by grants from the National Institutes of Health (R00 NS060996, R01 NS070911 and R01 DA031367), and the Edward Mallinckrodt Jr., Rita Allen and Brain and Behavior Research Foundations.\n\nPublished - fncir-07-00058.pdf
", "abstract": "Every day, we shift among various states of sleep and arousal to meet the many demands of our bodies and environment. A central puzzle in neurobiology is how the brain controls these behavioral states, which are essential to an animal's well-being and survival. Mammalian models have predominated sleep and arousal research, although in the past decade, invertebrate models have made significant contributions to our understanding of the genetic underpinnings of behavioral states. More recently, the zebrafish has emerged as a promising model system for sleep and arousal research. Here we review experimental evidence that the zebrafish, a diurnal vertebrate, exhibits fundamental behavioral and neurochemical characteristics of mammalian sleep and arousal. We also propose how specific advantages of the zebrafish can be harnessed to advance the field. These include tractable genetics to identify and manipulate molecular and cellular regulators of behavioral states, optical transparency to facilitate in vivo observation of neural structure and function, and amenability to high-throughput drug screens to discover novel therapies for neurological disorders.", "date": "2013-04-09", "date_type": "published", "publication": "Frontiers in Neural Circuits", "volume": "7", "publisher": "Frontiers Research Foundation", "pagerange": "Art. No. 58", "id_number": "CaltechAUTHORS:20130530-151659249", "issn": "1662-5110", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130530-151659249", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R00 NS060996" }, { "agency": "NIH", "grant_number": "R01 NS070911" }, { "agency": "NIH", "grant_number": "R01 DA031367" }, { "agency": "Edward Mallinckrodt Jr. Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Brain and Behavior Research Foundation" } ] }, "doi": "10.3389/fncir.2013.00058", "pmcid": "PMC3620505", "primary_object": { "basename": "fncir-07-00058.pdf", "url": "https://authors.library.caltech.edu/records/ms6ta-ykt68/files/fncir-07-00058.pdf" }, "resource_type": "article", "pub_year": "2013", "author_list": "Chiu, Cindy N. and Prober, David A." }, { "id": "https://authors.library.caltech.edu/records/0829p-9k457", "eprint_id": 38811, "eprint_status": "archive", "datestamp": "2023-08-19 14:34:07", "lastmod": "2023-10-23 23:30:07", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chen-Shijia", "name": { "family": "Chen", "given": "Shijia" } }, { "id": "Oikonomou-G", "name": { "family": "Oikonomou", "given": "Grigorios" }, "orcid": "0000-0001-6797-7375" }, { "id": "Chiu-Cindy-N", "name": { "family": "Chiu", "given": "Cindy N." } }, { "id": "Niles-B-J", "name": { "family": "Niles", "given": "Brett J." } }, { "id": "Liu-Justin", "name": { "family": "Liu", "given": "Justin" }, "orcid": "0000-0002-5338-6491" }, { "id": "Lee-Daniel-A", "name": { "family": "Lee", "given": "Daniel A." }, "orcid": "0000-0001-7411-2740" }, { "id": "Antoshechkin-I-A", "name": { "family": "Antoshechkin", "given": "Igor" }, "orcid": "0000-0002-9934-3040" }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" } ] }, "title": "A large-scale in vivo analysis reveals that TALENs are significantly more mutagenic than ZFNs generated using context-dependent assembly", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 The Author(s) 2013. Published by Oxford University Press.\nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/\nby-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.\nReceived October 23, 2012; Revised and Accepted December 5, 2012.\n\nFirst published online: January 8, 2013.\n\nThe authors thank Jason Stein for statistical assistance,\nScot Wolfe for sharing sequence alignment algorithms\nand Catherine Oikonomou for comments on the\nmanuscript.\nFunding: National Institutes of Health (NIH) [R00 NS060996, R01\nNS070911 and R01DA031367 to D.A.P., F31NS077842\nto S.C., F31NS077844 to J.L.]; Edward Mallinckrodt\nJr., Rita Allen and Brain and Behavior Research\nFoundations (to D.A.P.); Della Martin Fund (to D.A.P.\nand G.O.); Millard and Muriel Jacobs Genetics and\nGenomics Laboratory at the California Institute of\nTechnology. Funding for open access charge: NIH.\n\nPublished - Nucl._Acids_Res.-2013-Chen-2769-78.pdf
Supplemental Material - nar-02876-h-2012-File007.pdf
Supplemental Material - nar-02876-h-2012-File008.xlsx
", "abstract": "Zinc-finger nucleases (ZFNs) and TAL effector nucleases\n(TALENs) have been shown to induce\ntargeted mutations, but they have not been extensively\ntested in any animal model. Here, we describe\na large-scale comparison of ZFN and TALEN\nmutagenicity in zebrafish. Using deep sequencing,\nwe found that TALENs are significantly more likely\nto be mutagenic and induce an average of 10-fold\nmore mutations than ZFNs. We observed a strong\ncorrelation between somatic and germ-line mutagenicity,\nand identified germ line mutations using\nZFNs whose somatic mutations rates are well\nbelow the commonly used threshold of 1%. Guidelines\nthat have previously been proposed to predict\noptimal ZFN and TALEN target sites did not predict\nmutagenicity in vivo. However, we observed a significant\nnegative correlation between TALEN mutagenicity\nand the number of CpG repeats in TALEN\ntarget sites, suggesting that target site methylation\nmay explain the poor mutagenicity of some TALENs\nin vivo. The higher mutation rates and ability to\ntarget essentially any sequence make TALENs the\nsuperior technology for targeted mutagenesis in\nzebrafish, and likely other animal models.", "date": "2013-02", "date_type": "published", "publication": "Nucleic Acids Research", "volume": "41", "number": "4", "publisher": "Oxford University Press", "pagerange": "2769-2778", "id_number": "CaltechAUTHORS:20130605-105912475", "issn": "0305-1048", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130605-105912475", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R00 NS060996" }, { "agency": "NIH", "grant_number": "R01 NS070911" }, { "agency": "NIH", "grant_number": "R01DA031367" }, { "agency": "NIH", "grant_number": "F31NS077842" }, { "agency": "NIH", "grant_number": "F31NS077842" }, { "agency": "Edward Mallinckrodt Jr. Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Brain and Behavior Research Foundation" }, { "agency": "Della Martin Fund" }, { "agency": "Caltech Millard and Muriel Jacobs Genetics and Genomics Laboratory" } ] }, "doi": "10.1093/nar/gks1356", "pmcid": "PMC3575824", "primary_object": { "basename": "Nucl._Acids_Res.-2013-Chen-2769-78.pdf", "url": "https://authors.library.caltech.edu/records/0829p-9k457/files/Nucl._Acids_Res.-2013-Chen-2769-78.pdf" }, "related_objects": [ { "basename": "nar-02876-h-2012-File007.pdf", "url": "https://authors.library.caltech.edu/records/0829p-9k457/files/nar-02876-h-2012-File007.pdf" }, { "basename": "nar-02876-h-2012-File008.xlsx", "url": "https://authors.library.caltech.edu/records/0829p-9k457/files/nar-02876-h-2012-File008.xlsx" } ], "resource_type": "article", "pub_year": "2013", "author_list": "Chen, Shijia; Oikonomou, Grigorios; et el." }, { "id": "https://authors.library.caltech.edu/records/515n4-6jx58", "eprint_id": 102557, "eprint_status": "archive", "datestamp": "2023-08-19 09:51:10", "lastmod": "2023-10-20 00:18:01", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Pan-Y-Albert", "name": { "family": "Pan", "given": "Y. Albert" } }, { "id": "Choy-Margaret", "name": { "family": "Choy", "given": "Margaret" } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Schier-A-F", "name": { "family": "Schier", "given": "Alexander F." } } ] }, "title": "Robo2 determines subtype-specific axonal projections of trigeminal sensory neurons", "ispublished": "pub", "full_text_status": "public", "keywords": "Nociception, Somatosensory, TRPA1, Targeting, Axon guidance, Synaptogenesis, Zebrafish", "note": "\u00a9 2012 Company of Biologists. \n\nAccepted December 1, 2011. \n\nWe dedicate this study to C. B. Chien and thank him for the robo2 and Slit gene probes, robo2 (astray) mutant fish and for many thoughtful suggestions. We thank D. Yelon for the CHORI211-236I20 BAC clone; M. Meyer for the Syp:GFP-DSR plasmid; S. Zimmerman, J. Miller and K. Hurley for fish care; P. Huang, F. Imam, J. Kay, F. Merkle and X. Wang for critical comments on the manuscript; and members of the Schier laboratory for discussion. \n\nThis work was supported by a National Research Service Award (NRSA) postdoctoral fellowship from the National Institutes of Health [F32 NS057870 to Y.A.P.]; and research grants from the National Institutes of Health [R01 HD067140 and R01 NS049319 to A.F.S.]. Deposited in PMC for release after 12 months. \n\nThe authors declare no competing financial interests.\n\nPublished - 591.full.pdf
Supplemental Material - DEV076588FigS1.jpg
Supplemental Material - DEV076588FigS2.jpg
Supplemental Material - DEV076588FigS3.jpg
Supplemental Material - DEV076588FigS4.jpg
", "abstract": "How neurons connect to form functional circuits is central to the understanding of the development and function of the nervous system. In the somatosensory system, perception of sensory stimuli to the head requires specific connections between trigeminal sensory neurons and their many target areas in the central nervous system. Different trigeminal subtypes have specialized functions and downstream circuits, but it has remained unclear how subtype-specific axonal projection patterns are formed. Using zebrafish as a model system, we followed the development of two trigeminal sensory neuron subtypes: one that expresses trpa1b, a nociceptive channel important for sensing environmental chemicals; and a distinct subtype labeled by an islet1 reporter (Isl1SS). We found that Trpa1b and Isl1SS neurons have overall similar axon trajectories but different branching morphologies and distributions of presynaptic sites. Compared with Trpa1b neurons, Isl1SS neurons display reduced branch growth and synaptogenesis at the hindbrain-spinal cord junction. The subtype-specific morphogenesis of Isl1SS neurons depends on the guidance receptor Robo2. robo2 is preferentially expressed in the Isl1SS subset and inhibits branch growth and synaptogenesis. In the absence of Robo2, Isl1SS afferents acquire many of the characteristics of Trpa1b afferents. These results reveal that subtype-specific activity of Robo2 regulates subcircuit morphogenesis in the trigeminal sensory system.", "date": "2012-02", "date_type": "published", "publication": "Development", "volume": "139", "number": "3", "publisher": "Company of Biologists", "pagerange": "591-600", "id_number": "CaltechAUTHORS:20200415-105814073", "issn": "0950-1991", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200415-105814073", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32 NS057870" }, { "agency": "NIH", "grant_number": "R01 HD067140" }, { "agency": "NIH", "grant_number": "R01 NS049319" } ] }, "doi": "10.1242/dev.076588", "pmcid": "PMC3252355", "primary_object": { "basename": "591.full.pdf", "url": "https://authors.library.caltech.edu/records/515n4-6jx58/files/591.full.pdf" }, "related_objects": [ { "basename": "DEV076588FigS1.jpg", "url": "https://authors.library.caltech.edu/records/515n4-6jx58/files/DEV076588FigS1.jpg" }, { "basename": "DEV076588FigS2.jpg", "url": "https://authors.library.caltech.edu/records/515n4-6jx58/files/DEV076588FigS2.jpg" }, { "basename": "DEV076588FigS3.jpg", "url": "https://authors.library.caltech.edu/records/515n4-6jx58/files/DEV076588FigS3.jpg" }, { "basename": "DEV076588FigS4.jpg", "url": "https://authors.library.caltech.edu/records/515n4-6jx58/files/DEV076588FigS4.jpg" } ], "resource_type": "article", "pub_year": "2012", "author_list": "Pan, Y. Albert; Choy, Margaret; et el." }, { "id": "https://authors.library.caltech.edu/records/qtb06-h1n28", "eprint_id": 17944, "eprint_status": "archive", "datestamp": "2023-08-19 02:04:40", "lastmod": "2023-10-20 15:27:09", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Naumann-E-A", "name": { "family": "Naumann", "given": "Eva A." } }, { "id": "Kampff-A-R", "name": { "family": "Kampff", "given": "Adam R." } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Schier-A-F", "name": { "family": "Schier", "given": "Alexander F." } }, { "id": "Engert-F", "name": { "family": "Engert", "given": "Florian" } } ] }, "title": "Monitoring neural activity with bioluminescence during natural behavior", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2010 Nature Publishing Group. \n\nReceived 9 November 2009; accepted 22 February 2010; published online 21 March 2010. \n\nWe thank W. Hastings and T. Wilson for bountiful advice and discussion and generously providing an intensified CCD camera. We also thank L. Tricoire for the kind gift of the GFP-apoAequorin construct, M. Orger, A. Douglass, P. Ramdya, and members of the Engert and Schier laboratories for comments and advice, A. Douglass for N\u03b2t-gal4 vectors, P. Ramdya for providing the nacre strains and B. Obama for his stimulation package. We thank S. Zimmerman, K. Hurley, and J. Miller for excellent zebrafish care. This work was funded by the McKnight Foundation (F.E.), the Harvard Mind, Brain and Behavior post-doctoral fellows program (A.R.K.), and the US National Institutes of Health (A.F.S. and D.A.P.). \n\nAuthor Contributions: E.A.N. and A.R.K. designed the assay and performed the experiments. E.A.N., A.R.K. and F.E. analyzed the data. D.A.P. and A.F.S. generated the HCRT\u2013GFP-apoAequorin transgenic line and assisted with behavioral analysis. E.A.N., A.R.K., D.A.P., A.F.S. and F.E. prepared the manuscript. E.A.N. suffered the most.\n\nPublished - NatNeuro.pdf
Accepted Version - nihms181675.pdf
Supplemental Material - nn.2518-S1.pdf
", "abstract": "Existing techniques for monitoring neural activity in awake, freely behaving vertebrates are invasive and difficult to target to genetically identified neurons. We used bioluminescence to non-invasively monitor the activity of genetically specified neurons in freely behaving zebrafish. Transgenic fish with the Ca^(2+)-sensitive photoprotein green fluorescent protein (GFP)-Aequorin in most neurons generated large and fast bioluminescent signals that were related to neural activity, neuroluminescence, which could be recorded continuously for many days. To test the limits of this technique, we specifically targeted GFP-Aequorin to the hypocretin-positive neurons of the hypothalamus. We found that neuroluminescence generated by this group of ~20 neurons was associated with periods of increased locomotor activity and identified two classes of neural activity corresponding to distinct swim latencies. Our neuroluminescence assay can report, with high temporal resolution and sensitivity, the activity of small subsets of neurons during unrestrained behavior.", "date": "2010-04", "date_type": "published", "publication": "Nature Neuroscience", "volume": "13", "number": "4", "publisher": "Nature Publishing Group", "pagerange": "513-522", "id_number": "CaltechAUTHORS:20100412-134749684", "issn": "1097-6256", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100412-134749684", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "McKnight Foundation" }, { "agency": "Harvard Mind, Brain and Behavior post-doctoral fellows" }, { "agency": "NIH" } ] }, "doi": "10.1038/nn.2518", "pmcid": "PMC2846983", "primary_object": { "basename": "nn.2518-S1.pdf", "url": "https://authors.library.caltech.edu/records/qtb06-h1n28/files/nn.2518-S1.pdf" }, "related_objects": [ { "basename": "NatNeuro.pdf", "url": "https://authors.library.caltech.edu/records/qtb06-h1n28/files/NatNeuro.pdf" }, { "basename": "nihms181675.pdf", "url": "https://authors.library.caltech.edu/records/qtb06-h1n28/files/nihms181675.pdf" } ], "resource_type": "article", "pub_year": "2010", "author_list": "Naumann, Eva A.; Kampff, Adam R.; et el." }, { "id": "https://authors.library.caltech.edu/records/s77vp-61g52", "eprint_id": 60230, "eprint_status": "archive", "datestamp": "2023-08-19 01:27:36", "lastmod": "2023-10-24 15:27:48", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rihel-J", "name": { "family": "Rihel", "given": "Jason" } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Arvanites-A", "name": { "family": "Arvanites", "given": "Anthony" } }, { "id": "Lam-Kelvin", "name": { "family": "Lam", "given": "Kelvin" } }, { "id": "Zimmerman-S", "name": { "family": "Zimmerman", "given": "Steven" } }, { "id": "Jang-Sumin", "name": { "family": "Jang", "given": "Sumin" } }, { "id": "Haggarty-S-J", "name": { "family": "Haggarty", "given": "Stephen J." } }, { "id": "Kokel-D", "name": { "family": "Kokel", "given": "David" } }, { "id": "Rubin-L-L", "name": { "family": "Rubin", "given": "Lee L." } }, { "id": "Peterson-R-T", "name": { "family": "Peterson", "given": "Randall T." } }, { "id": "Schier-A-F", "name": { "family": "Schier", "given": "Alexander F." } } ] }, "title": "Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2010 American Association for the Advancement of Science. \n\nReceived for publication 8 October 2009. Accepted for publication 11 December 2009. \n\nWe thank J. Dowling, D. Milan, and G. Vanderlaan for suggestions and reagents and D. Schoppik, G. Uhl, and I. Woods for critical reading of the manuscript. Supported by a Bristol-Myers Squibb postdoctoral fellowship of the Life Sciences Research Foundation (J.R.), a Helen Hay Whitney Foundation postdoctoral fellowship (D.A.P.), a NIH Pathway to Independence grant (D.A.P.), the Stanley Medical Research Institute (S.J.H.), the Harvard Stem Cell Institute (L.L.R.), NIH grants MH086867 and MH085205 (R.T.P.), and grants from NIH and the McKnight Endowment Fund for Neuroscience (A.F.S.). L.L.R. is a founder of iPierian Inc., a biotechnology company, and is a member of its scientific advisory board.\n\nAccepted Version - nihms178948.pdf
Supplemental Material - Rihel.SOM.pdf
", "abstract": "A major obstacle for the discovery of psychoactive drugs is the inability to predict how small molecules will alter complex behaviors. We report the development and application of a high-throughput, quantitative screen for drugs that alter the behavior of larval zebrafish. We found that the multidimensional nature of observed phenotypes enabled the hierarchical clustering of molecules according to shared behaviors. Behavioral profiling revealed conserved functions of psychotropic molecules and predicted the mechanisms of action of poorly characterized compounds. In addition, behavioral profiling implicated new factors such as ether-a-go-go\u2013related gene (ERG) potassium channels and immunomodulators in the control of rest and locomotor activity. These results demonstrate the power of high-throughput behavioral profiling in zebrafish to discover and characterize psychotropic drugs and to dissect the pharmacology of complex behaviors.", "date": "2010-01-15", "date_type": "published", "publication": "Science", "volume": "327", "number": "5963", "publisher": "American Association for the Advancement of Science", "pagerange": "348-351", "id_number": "CaltechAUTHORS:20150914-145343001", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150914-145343001", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Bristol-Myers Squibb" }, { "agency": "Life Sciences Research Foundation" }, { "agency": "Helen Hay Whitney Foundation" }, { "agency": "NIH Pathway to Independence" }, { "agency": "Stanley Medical Research Institute" }, { "agency": "Harvard Stem Cell Institute" }, { "agency": "NIH", "grant_number": "MH086867" }, { "agency": "NIH", "grant_number": "MH085205" }, { "agency": "McKnight Endowment Fund for Neuroscience" }, { "agency": "NIH" } ] }, "doi": "10.1126/science.1183090", "pmcid": "PMC2830481", "primary_object": { "basename": "nihms178948.pdf", "url": "https://authors.library.caltech.edu/records/s77vp-61g52/files/nihms178948.pdf" }, "related_objects": [ { "basename": "Rihel.SOM.pdf", "url": "https://authors.library.caltech.edu/records/s77vp-61g52/files/Rihel.SOM.pdf" } ], "resource_type": "article", "pub_year": "2010", "author_list": "Rihel, Jason; Prober, David A.; et el." }, { "id": "https://authors.library.caltech.edu/records/s8f62-x5j33", "eprint_id": 60356, "eprint_status": "archive", "datestamp": "2023-08-22 13:17:17", "lastmod": "2023-10-24 16:28:14", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Zimmerman-S", "name": { "family": "Zimmerman", "given": "Steven" } }, { "id": "Myers-B-R", "name": { "family": "Myers", "given": "Benjamin R." } }, { "id": "McDermott-B-M-Jr", "name": { "family": "McDermott", "given": "Brian M., Jr." } }, { "id": "Kim-Seok-Hyung", "name": { "family": "Kim", "given": "Seok-Hyung" } }, { "id": "Caron-S", "name": { "family": "Caron", "given": "Sophie" } }, { "id": "Rihel-J", "name": { "family": "Rihel", "given": "Jason" } }, { "id": "Solnica-Krezel-L", "name": { "family": "Solnica-Krezel", "given": "Lilianna" } }, { "id": "Julius-D", "name": { "family": "Julius", "given": "David" } }, { "id": "Hudspeth-A-J", "name": { "family": "Hudspeth", "given": "A. J." } }, { "id": "Schier-A-F", "name": { "family": "Schier", "given": "Alexander F." } } ] }, "title": "Zebrafish TRPA1 Channels Are Required for Chemosensation But Not for Thermosensation or Mechanosensory Hair Cell Function", "ispublished": "pub", "full_text_status": "public", "keywords": "nociception; temperature; mechanosensory; chemosensory; behavior; hair cell", "note": "\u00a9 2008 Society for Neuroscience. For the first six months after publication SfN's license will be exclusive. Beginning six months after publication the Work will be made freely available to the public on SfN's website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/). \n\nReceived June 16, 2008. Revision received August 22, 2008. Accepted August 24, 2008. \n\nThis work was supported by National Institutes of Health (NIH) Grants DC00241 (A.J.H.), NS055799 (D.J.), and NS049319 (A.F.S.); the Zebrafish Vanderbilt Initiative Academic Venture Capital Fund (L.S.-K.); the University Hospitals Case Medical Center\u2212Center for Clinical Research and Technology (B.M.M.); and the Case Research Institute Vision Fund (B.M.M.). D.A.P. was supported by a fellowship from the Helen Hay Whitney Foundation and an NIH Pathway to Independence award. B.R.M. is a Predoctoral Fellow of the American Heart Association. B.M.M. is supported by a Basil O'Connor Starter Scholar Research Award from the March of Dimes. J.R. is a Bristol-Myers Squibb Life Sciences Research Foundation Fellow. A.J.H. is an Investigator of the Howard Hughes Medical Institute. We thank Drs. Cuppen, de Bruin, and Plasterk (Hubrecht laboratory) and Drs. Kettleborough and Stemple (Welcome Trust Sanger Institute) for providing the zebrafish trpa1a knock-out mutant (ZF-MODELS Integrated Project; contract number LSHG-CT-2003-503496; funded by the European Commission). We thank B. Fabella for providing the software for recording microphonic potentials, M. Vologodskaia and C. Fernando for genotyping larvae used in microphonic potential recordings and FM1-43 experiments, M. West for performing FM1-43 injections, and David Schoppik and Ian Woods for comments on this manuscript.\n\nPublished - 10102.full.pdf
Supplemental Material - Figure_S1.pdf
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Supplemental Material - Figure_S7.pdf
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Supplemental Material - Supplemental_Legend.pdf
", "abstract": "Transient receptor potential (TRP) ion channels have been implicated in detecting chemical, thermal, and mechanical stimuli in organisms ranging from mammals to Caenorhabditis elegans. It is well established that TRPA1 detects and mediates behavioral responses to chemical irritants. However, the role of TRPA1 in detecting thermal and mechanical stimuli is controversial. To further clarify the functions of TRPA1 channels in vertebrates, we analyzed their roles in zebrafish. The two zebrafish TRPA1 paralogs are expressed in sensory neurons and are activated by several chemical irritants in vitro. High-throughput behavioral analyses of trpa1a and trpa1b mutant larvae indicate that TRPA1b is necessary for behavioral responses to these chemical irritants. However, TRPA1 paralogs are not required for behavioral responses to temperature changes or for mechanosensory hair cell function in the inner ear or lateral line. These results support a role for zebrafish TRPA1 in chemical but not thermal or mechanical sensing, and establish a high-throughput system to identify genes and small molecules that modulate chemosensation, thermosensation, and mechanosensation.", "date": "2008-10-01", "date_type": "published", "publication": "Journal of Neuroscience", "volume": "28", "number": "40", "publisher": "Society for Neuroscience", "pagerange": "10102-10110", "id_number": "CaltechAUTHORS:20150918-155039693", "issn": "0270-6474", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150918-155039693", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "DC00241" }, { "agency": "NIH", "grant_number": "NS055799" }, { "agency": "NIH", "grant_number": "NS049319" }, { "agency": "Zebrafish Vanderbilt Initiative Academic Venture Capital Fund" }, { "agency": "University Hospitals Case Medical Center\u2212Center for Clinical Research and Technology" }, { "agency": "Case Research Institute Vision Fund" }, { "agency": "Helen Hay Whitney Foundation" }, { "agency": "NIH Pathway to Independence Award" }, { "agency": "American Heart Association (AHA) Predoctoral Fellowship" }, { "agency": "March of Dimes" }, { "agency": "Life Sciences Research Foundation" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1523/JNEUROSCI.2740-08.2008", "pmcid": "PMC2728686", "primary_object": { "basename": "Figure_S4.pdf", "url": "https://authors.library.caltech.edu/records/s8f62-x5j33/files/Figure_S4.pdf" }, "related_objects": [ { "basename": "Figure_S5.pdf", "url": "https://authors.library.caltech.edu/records/s8f62-x5j33/files/Figure_S5.pdf" }, { "basename": "Figure_S6.pdf", "url": "https://authors.library.caltech.edu/records/s8f62-x5j33/files/Figure_S6.pdf" }, { "basename": "Figure_S7.pdf", "url": "https://authors.library.caltech.edu/records/s8f62-x5j33/files/Figure_S7.pdf" }, { "basename": "Movie_S2.mov", "url": "https://authors.library.caltech.edu/records/s8f62-x5j33/files/Movie_S2.mov" }, { "basename": "10102.full.pdf", "url": "https://authors.library.caltech.edu/records/s8f62-x5j33/files/10102.full.pdf" }, { "basename": "Figure_S1.pdf", "url": "https://authors.library.caltech.edu/records/s8f62-x5j33/files/Figure_S1.pdf" }, { "basename": "Figure_S2.pdf", "url": "https://authors.library.caltech.edu/records/s8f62-x5j33/files/Figure_S2.pdf" }, { "basename": "Figure_S3.pdf", "url": "https://authors.library.caltech.edu/records/s8f62-x5j33/files/Figure_S3.pdf" }, { "basename": "Movie_S1.mov", "url": "https://authors.library.caltech.edu/records/s8f62-x5j33/files/Movie_S1.mov" }, { "basename": "Supplemental_Legend.pdf", "url": "https://authors.library.caltech.edu/records/s8f62-x5j33/files/Supplemental_Legend.pdf" } ], "resource_type": "article", "pub_year": "2008", "author_list": "Prober, David A.; Zimmerman, Steven; et el." }, { "id": "https://authors.library.caltech.edu/records/kp18h-t6y75", "eprint_id": 102560, "eprint_status": "archive", "datestamp": "2023-08-22 10:23:51", "lastmod": "2023-10-20 00:18:10", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "O'Keefe-D-D", "name": { "family": "O'Keefe", "given": "David D." } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Moyle-P-S", "name": { "family": "Moyle", "given": "Patrick S." } }, { "id": "Rickoll-W-L", "name": { "family": "Rickoll", "given": "Wayne L." } }, { "id": "Edgar-B-A", "name": { "family": "Edgar", "given": "Bruce A." } } ] }, "title": "Egfr/Ras signaling regulates DE-cadherin/Shotgun localization to control vein morphogenesis in the Drosophila wing", "ispublished": "pub", "full_text_status": "public", "keywords": "Drosophila; Cell adhesion; Adherens junction; Wing development; Wing vein; E-cadherin; Ras; Egfr", "note": "\u00a9 2007 Elsevier Inc. \n\nReceived 13 March 2007, Revised 1 August 2007, Accepted 2 August 2007, Available online 9 August 2007. \n\nWe would like to thank Seth Blair, Pernille Rorth, Ernst Hafen, Jose de Celis, Marta Llimargas, Celeste Berg, Hannele Ruohola-Baker, The Developmental Studies Hybridoma Bank, and the Bloomington Drosophila Stock Center for reagents. We are particularly grateful to Ryu Ueda and his colleagues at the National Institute of Genetics in Japan for generation of the UAS-RNAi transgenes used in this study. Thanks to the University of Puget Sound and Dr. Scott Weatherwax for supporting the UPS Weatherwax Electron microscopy Lab. Thanks to Julio Vazquez, Dave McDonald, and Adrian Quintanilla for help with confocal microscopy. Finally, thanks to Leslie Saucedo, Steve \"Jahman\" Lee, and the entire Edgar lab for advice and entertainment. This work was supported by NIH U56 CA096288 to Beti Thompson, NIH R01 GM51186 to B.A.E., and an American Cancer Society Postdoctoral Fellowship to D.D.O.\n\nAccepted Version - nihms33729.pdf
Supplemental Material - 1-s2.0-S0012160607012456-mmc1.doc
", "abstract": "Egfr/Ras signaling promotes vein cell fate specification in the developing Drosophila wing. While the importance of Ras signaling in vein determination has been extensively documented, the mechanisms linking Ras activity to vein differentiation remain unclear. We found that Ras signaling regulates both the levels and subcellular localization of the cell adhesion molecule DE-cadherin/Shotgun (Shg) in the differentiating wing epithelium. High Ras activity in presumptive vein cells directs the apical localization of Shg containing adherens junctions, whereas low Ras activity in intervein cells allows Shg to relocalize basally. These alterations in Shg-mediated adhesion control cell shape changes that are essential for vein morphogenesis. While Decapentaplegic (Dpp) acts downstream of Ras to maintain vein cell identity in the pupal wing, our results indicate that Ras controls Shg localization via a Dpp-independent mechanism. Ras, therefore, regulates both the transcriptional responses necessary for vein cell identity, and the cell adhesive changes that determine vein and intervein cell morphology.", "date": "2007-11-01", "date_type": "published", "publication": "Developmental Biology", "volume": "311", "number": "1", "publisher": "Elsevier", "pagerange": "25-39", "id_number": "CaltechAUTHORS:20200415-122447337", "issn": "0012-1606", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200415-122447337", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "U56 CA096288" }, { "agency": "NIH", "grant_number": "R01 GM51186" }, { "agency": "American Cancer Society" } ] }, "doi": "10.1016/j.ydbio.2007.08.003", "pmcid": "PMC2128780", "primary_object": { "basename": "1-s2.0-S0012160607012456-mmc1.doc", "url": "https://authors.library.caltech.edu/records/kp18h-t6y75/files/1-s2.0-S0012160607012456-mmc1.doc" }, "related_objects": [ { "basename": "nihms33729.pdf", "url": "https://authors.library.caltech.edu/records/kp18h-t6y75/files/nihms33729.pdf" } ], "resource_type": "article", "pub_year": "2007", "author_list": "O'Keefe, David D.; Prober, David A.; et el." }, { "id": "https://authors.library.caltech.edu/records/y5e5w-twc13", "eprint_id": 60352, "eprint_status": "archive", "datestamp": "2023-08-22 07:52:42", "lastmod": "2023-10-24 16:28:00", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Rihel-J", "name": { "family": "Rihel", "given": "Jason" } }, { "id": "Onah-A-A", "name": { "family": "Onah", "given": "Anthony A." } }, { "id": "Sung-Rou-Jia", "name": { "family": "Sung", "given": "Rou-Jia" } }, { "id": "Schier-A-F", "name": { "family": "Schier", "given": "Alexander F." } } ] }, "title": "Hypocretin/Orexin Overexpression Induces An Insomnia-Like Phenotype in Zebrafish", "ispublished": "pub", "full_text_status": "public", "keywords": "hypocretin; orexin; sleep; insomnia; circadian rhythm; zebrafish", "note": "\u00a9 2006 Society for Neuroscience. Beginning six months after publication the Work will be made freely available to the public on SfN's website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/). \n\nReceived October 4, 2006. Revision received November 9, 2006. Accepted November 13, 2006. \n\nThis work was supported by grants from the National Institutes of Health and the McKnight Endowment Fund for Neuroscience (A.F.S.). D.A.P. was supported by a fellowship from the Helen Hay Whitney Foundation. J.R. is a Bristol-Myers Squibb Fellow of the Life Sciences Research Foundation. We thank Wolfgang Driever, Su Guo, Shin-Ichi Higashijima, and Steve Wilson for providing in situ probes, Steven Zimmerman for technical assistance, Amir Karger for assistance with data analysis, Patrick Mabray and Irina Zhdanova for advice on behavioral assays, and Sebastian Kraves for comments on this manuscript.\n\nPublished - 13400.full.pdf
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Supplemental Material - Supplemental_Fig_6.pdf
Supplemental Material - Supplemental_Fig_7.pdf
Supplemental Material - Supplemental_Fig_8.pdf
Supplemental Material - Supplemental_Fig_9.pdf
Supplemental Material - Supplemental_Figure_Legends.pdf
", "abstract": "As many as 10% of humans suffer chronic sleep disturbances, yet the genetic mechanisms that regulate sleep remain essentially unknown. It is therefore crucial to develop simple and cost-effective vertebrate models to study the genetic regulation of sleep. The best characterized mammalian sleep/wake regulator is hypocretin/orexin (Hcrt), whose loss results in the sleep disorder narcolepsy and that has also been implicated in feeding behavior, energy homeostasis, thermoregulation, reward seeking, addiction, and maternal behavior. Here we report that the expression pattern and axonal projections of embryonic and larval zebrafish Hcrt neurons are strikingly similar to those in mammals. We show that zebrafish larvae exhibit robust locomotive sleep/wake behaviors as early as the fifth day of development and that Hcrt overexpression promotes and consolidates wakefulness and inhibits rest. Similar to humans with insomnia, Hcrt-overexpressing larvae are hyperaroused and have dramatically reduced abilities to initiate and maintain rest at night. Remarkably, Hcrt function is modulated by but does not require normal circadian oscillations in locomotor activity. Our zebrafish model of Hcrt overexpression indicates that the ancestral function of Hcrt is to promote locomotion and inhibit rest and will facilitate the discovery of neural circuits, genes, and drugs that regulate Hcrt function and sleep.", "date": "2006-12-20", "date_type": "published", "publication": "Journal of Neuroscience", "volume": "26", "number": "51", "publisher": "Society for Neuroscience", "pagerange": "13400-13410", "id_number": "CaltechAUTHORS:20150918-153127266", "issn": "0270-6474", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150918-153127266", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "McKnight Endowment Fund for Neuroscience" }, { "agency": "Helen Hay Whitney Foundation" }, { "agency": "Life Sciences Research Foundation" } ] }, "doi": "10.1523/JNEUROSCI.4332-06.2006", "pmcid": "PMC6675014", "primary_object": { "basename": "Supplemental_Fig_3.pdf", "url": "https://authors.library.caltech.edu/records/y5e5w-twc13/files/Supplemental_Fig_3.pdf" }, "related_objects": [ { "basename": "Supplemental_Fig_5.pdf", "url": "https://authors.library.caltech.edu/records/y5e5w-twc13/files/Supplemental_Fig_5.pdf" }, { "basename": "Supplemental_Fig_7.pdf", "url": "https://authors.library.caltech.edu/records/y5e5w-twc13/files/Supplemental_Fig_7.pdf" }, { "basename": "Supplemental_Fig_8.pdf", "url": "https://authors.library.caltech.edu/records/y5e5w-twc13/files/Supplemental_Fig_8.pdf" }, { "basename": "13400.full.pdf", "url": "https://authors.library.caltech.edu/records/y5e5w-twc13/files/13400.full.pdf" }, { "basename": "Supplemental_Fig_1.pdf", "url": "https://authors.library.caltech.edu/records/y5e5w-twc13/files/Supplemental_Fig_1.pdf" }, { "basename": "Supplemental_Fig_2.pdf", "url": "https://authors.library.caltech.edu/records/y5e5w-twc13/files/Supplemental_Fig_2.pdf" }, { "basename": "Supplemental_Fig_4.pdf", "url": "https://authors.library.caltech.edu/records/y5e5w-twc13/files/Supplemental_Fig_4.pdf" }, { "basename": "Supplemental_Fig_6.pdf", "url": "https://authors.library.caltech.edu/records/y5e5w-twc13/files/Supplemental_Fig_6.pdf" }, { "basename": "Supplemental_Fig_9.pdf", "url": "https://authors.library.caltech.edu/records/y5e5w-twc13/files/Supplemental_Fig_9.pdf" }, { "basename": "Supplemental_Figure_Legends.pdf", "url": "https://authors.library.caltech.edu/records/y5e5w-twc13/files/Supplemental_Figure_Legends.pdf" } ], "resource_type": "article", "pub_year": "2006", "author_list": "Prober, David A.; Rihel, Jason; et el." }, { "id": "https://authors.library.caltech.edu/records/hefhj-2k112", "eprint_id": 102562, "eprint_status": "archive", "datestamp": "2023-08-21 23:41:21", "lastmod": "2023-10-20 00:18:15", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Edgar-B-A", "name": { "family": "Edgar", "given": "Bruce A." } } ] }, "title": "Interactions between Ras1, dMyc, and dPI3K signaling in the developing Drosophila wing", "ispublished": "pub", "full_text_status": "public", "keywords": "Ras; Myc; PI3K; Drosophila; cell growth; cell cycle", "note": "\u00a9 2002 by Cold Spring Harbor Laboratory Press. \n\nReceived March 14, 2002. Accepted July 3, 2002. \n\nWe thank Wendy Lockwood and Steve Cohen for providing us with the tGPH stock prior to publication. We also thank Celeste Berg, Ulrike Gaul, Ernst Hafen, Felix Karim, Sally Leevers, Hideyuki Okano, and Trudy Schupbach for fly stocks; Robert Eisenman, Rafael Fernandez, Peter Gallant, Juergen Knoblich, and Cynthia Yost for antibodies; Aida de la Cruz, Cristina Martin-Castellanos, Lenora Loo, Cecilia De Lorenzo, Amir Oryan, Kelly Plow, and Cynthia Yost for sharing unpublished data; Celeste Berg, Robert Eisenman, Savraj Grewal, and Tom Neufeld for comments on the manuscript; and members of the Edgar laboratory for helpful discussions during the course of this work. D.A.P. was a predoctoral fellow of the National Science Foundation and the Molecular Training Program in Cancer Research. Supported by NIH GMS R01-51186. \n\nThe publication costs of this article were defrayed in part by payment of page charges. This article must therefore be hereby marked \"advertisement\" in accordance with 18 USC section 1734 solely to indicate this fact.\n\nPublished - Genes_Dev.-2002-Prober-2286-99.pdf
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", "abstract": "The Ras GTPase links extracellular signals to intracellular mechanisms that control cell growth, the cell cycle, and cell identity. An activated form of Drosophila Ras (Ras^(V12)) promotes these processes in the developing wing, but the effector pathways involved are unclear. Here, we present evidence indicating that Ras^(V12) promotes cell growth and G\u2081/S progression by increasing dMyc protein levels and activating dPI3K signaling, and that it does so via separate effector pathways. We also show that endogenous Ras is required to maintain normal levels of dMyc, but not dPI3K signaling during wing development. Finally, we show that induction of dMyc and regulation of cell identity are separable effects of Raf/MAPK signaling. These results suggest that Ras may only affect PI3K signaling when mutationally activated, such as in Ras^(V12)-transformed cells, and provide a basis for understanding the synergy between Ras and other growth-promoting oncogenes in cancer.", "date": "2002-09-01", "date_type": "published", "publication": "Genes and Development", "volume": "16", "number": "17", "publisher": "Cold Spring Harbor Laboratory Press", "pagerange": "2286-2299", "id_number": "CaltechAUTHORS:20200415-123439548", "issn": "0890-9369", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200415-123439548", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF Predoctoral Fellowship" }, { "agency": "NIH", "grant_number": "GMS R01-51186" } ] }, "doi": "10.1101/gad.991102", "pmcid": "PMC186666", "primary_object": { "basename": "ProberSuppMat.doc", "url": "https://authors.library.caltech.edu/records/hefhj-2k112/files/ProberSuppMat.doc" }, "related_objects": [ { "basename": "fig1.jpg", "url": "https://authors.library.caltech.edu/records/hefhj-2k112/files/fig1.jpg" }, { "basename": "fig2.jpg", "url": "https://authors.library.caltech.edu/records/hefhj-2k112/files/fig2.jpg" }, { "basename": "fig3.jpg", "url": "https://authors.library.caltech.edu/records/hefhj-2k112/files/fig3.jpg" }, { "basename": "fig4.jpg", "url": "https://authors.library.caltech.edu/records/hefhj-2k112/files/fig4.jpg" }, { "basename": "fig5.jpg", "url": "https://authors.library.caltech.edu/records/hefhj-2k112/files/fig5.jpg" }, { "basename": "fig6.jpg", "url": "https://authors.library.caltech.edu/records/hefhj-2k112/files/fig6.jpg" }, { "basename": "Genes_Dev.-2002-Prober-2286-99.pdf", "url": "https://authors.library.caltech.edu/records/hefhj-2k112/files/Genes_Dev.-2002-Prober-2286-99.pdf" } ], "resource_type": "article", "pub_year": "2002", "author_list": "Prober, David A. and Edgar, Bruce A." }, { "id": "https://authors.library.caltech.edu/records/hk47c-7an77", "eprint_id": 102564, "eprint_status": "archive", "datestamp": "2023-08-21 22:00:35", "lastmod": "2023-10-20 00:18:19", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Edgar-B-A", "name": { "family": "Edgar", "given": "Bruce A." } } ] }, "title": "Growth regulation by oncogenes \u2014 new insights from model organisms", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Oncogene; Growth; Cell cycle; Cell proliferation; Model organism; Development", "note": "\u00a9 2001 Elsevier Science Ltd. \n\nAvailable online 9 January 2001. \n\nWe thank Ed Giniger, Sally Leevers, Piotr Sicinski, and George Thomas for helpful discussions and comments on the manuscript.", "abstract": "A great deal of work has focused on how oncogenes regulate the cell cycle during normal development and in cancer, yet their roles in regulating cell growth have been largely unexplored. Recent work in several model organisms has demonstrated that homologs of several oncogenes regulate cell growth and has suggested that some of the effects of oncogenes on the cell cycle may be a result of growth promotion. These studies have also suggested how growth and cell-cycle progression may be coupled.", "date": "2001-02-01", "date_type": "published", "publication": "Current Opinion in Genetics and Development", "volume": "11", "number": "1", "publisher": "Elsevier", "pagerange": "19-26", "id_number": "CaltechAUTHORS:20200415-132631728", "issn": "0959-437X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200415-132631728", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1016/s0959-437x(00)00151-9", "resource_type": "article", "pub_year": "2001", "author_list": "Prober, David A. and Edgar, Bruce A." }, { "id": "https://authors.library.caltech.edu/records/6bvxd-je139", "eprint_id": 102565, "eprint_status": "archive", "datestamp": "2023-08-19 05:24:44", "lastmod": "2023-10-20 00:18:23", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Edgar-B-A", "name": { "family": "Edgar", "given": "Bruce A." } } ] }, "title": "Ras1 Promotes Cellular Growth in the Drosophila Wing", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2000 Cell Press. \n\nReceived 4 August 1999, Revised 11 January 2000, Available online 11 April 2001. \n\nWe thank Celeste Berg, Peter Gallant, Felix Karim, and Denise Montell for fly stocks; Robert Eisenman, Peter Gallant, and Helena Richardson for antibodies; Aida de la Cruz, Mary Kay Dolejsi (grant #5P30CA15704\u201326), Adrian Quintanilla, and the Fred Hutchinson Cancer Research Center Flow Cytometry and Image Analysis facilities for technical assistance; and Jon Cooper, Tom Neufeld, and members of the Edgar lab for helpful advice, discussions, and comments on the manuscript. D. A. P. is a National Science Foundation predoctoral fellow, and B. A. E. is a Rita Allen Scholar. This work supported by the National Institutes of Health (GM51186).\n\nPublished - 1-s2.0-S0092867400806790-main.pdf
", "abstract": "The Ras GTPase links extracellular mitogens to intracellular mechanisms that control cell proliferation. To understand how Ras regulates proliferation in vivo, we activated or inactivated Ras in cell clones in the developing Drosophila wing. Cells lacking Ras were smaller, had reduced growth rates, accumulated in G1, and underwent apoptosis due to cell competition. Conversely, activation of Ras increased cell size and growth rates and promoted G1/S transitions. Ras upregulated the growth driver dMyc, and both Ras and dMyc increased levels of cyclin E posttranscriptionally. We propose that Ras primarily promotes growth and that growth is coupled to G1/S progression via cyclin E. Interestingly, upregulation of growth by Ras did not deregulate G2/M progression or a developmentally regulated cell cycle exit.", "date": "2000-02-18", "date_type": "published", "publication": "Cell", "volume": "100", "number": "4", "publisher": "Elsevier", "pagerange": "435-446", "id_number": "CaltechAUTHORS:20200415-135140841", "issn": "0092-8674", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200415-135140841", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "5P30CA15704-26" }, { "agency": "NSF Predoctoral Fellowship" }, { "agency": "Rita Allen Foundation" }, { "agency": "NIH", "grant_number": "GM51186" } ] }, "doi": "10.1016/s0092-8674(00)80679-0", "primary_object": { "basename": "1-s2.0-S0092867400806790-main.pdf", "url": "https://authors.library.caltech.edu/records/6bvxd-je139/files/1-s2.0-S0092867400806790-main.pdf" }, "resource_type": "article", "pub_year": "2000", "author_list": "Prober, David A. and Edgar, Bruce A." }, { "id": "https://authors.library.caltech.edu/records/seya4-99f05", "eprint_id": 102566, "eprint_status": "archive", "datestamp": "2023-08-19 04:43:31", "lastmod": "2023-10-20 00:18:25", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Johnston-L-A", "name": { "family": "Johnston", "given": "Laura A." } }, { "id": "Prober-D-A", "name": { "family": "Prober", "given": "David A." }, "orcid": "0000-0002-7371-4675" }, { "id": "Edgar-B-A", "name": { "family": "Edgar", "given": "Bruce A." } }, { "id": "Eisenman-R-N", "name": { "family": "Eisenman", "given": "Robert N." } }, { "id": "Gallant-P", "name": { "family": "Gallant", "given": "Peter" } } ] }, "title": "Drosophila myc Regulates Cellular Growth during Development", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 1999 Cell Press. \n\nReceived 9 June 1999, Revised 11 August 1999. \n\nWe thank members of the Edgar and Eisenman labs for discussions during the course of the work; S. Parkhurst for advice and resources; A. de la Cruz, P. F. Cheng, A. Berger, L. Caldwell, and K. Seidel for technical assistance; and M. Groudine, E. Hafen, T. Neufeld, and J. Roberts for comments on the manuscript. Work in the Edgar lab is supported by the National Institutes of Health, and support for the Eisenman lab comes from the National Cancer Institute. L. A. J. was supported by NIH funding to G. Schubiger and P. G. by the Swiss National Science Foundation. B. A. E. is a Rita Allen Scholar, and R. N. E. is a Research Professor of the American Cancer Society.", "abstract": "Transcription factors of the Myc proto-oncogene family promote cell division, but how they do this is poorly understood. Here we address the functions of Drosophila Myc (dMyc) during development. Using mosaic analysis in the fly wing, we show that loss of dMyc retards cellular growth (accumulation of cell mass) and reduces cell size, whereas dMyc overproduction increases growth rates and cell size. dMyc-induced growth promotes G1/S progression but fails to accelerate cell division because G2/M progression is independently controlled by Cdc25/String. We also show that the secreted signal Wingless patterns growth in the wing primordium by modulating dMyc expression. Our results indicate that dMyc links patterning signals to cell division by regulating primary targets involved in cellular growth and metabolism.", "date": "1999-09-17", "date_type": "published", "publication": "Cell", "volume": "98", "number": "6", "publisher": "Elsevier", "pagerange": "779-790", "id_number": "CaltechAUTHORS:20200415-141031630", "issn": "0092-8674", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200415-141031630", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH" }, { "agency": "National Cancer Institute" }, { "agency": "Swiss National Science Foundation (SNSF)" }, { "agency": "Rita Allen Foundation" }, { "agency": "American Cancer Society" } ] }, "doi": "10.1016/s0092-8674(00)81512-3", "resource_type": "article", "pub_year": "1999", "author_list": "Johnston, Laura A.; Prober, David A.; et el." } ]