[ { "id": "authors:mc9j9-cf864", "collection": "authors", "collection_id": "mc9j9-cf864", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230223-183928700.3", "type": "article", "title": "Homologous gene regulatory networks control development of apical organs and brains in Bilateria", "author": [ { "family_name": "Feuda", "given_name": "Roberto", "orcid": "0000-0003-0857-1732", "clpid": "Feuda-Roberto" }, { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" } ], "abstract": "Apical organs are relatively simple larval nervous systems. The extent to which apical organs are evolutionarily related to the more complex nervous systems of other animals remains unclear. To identify common developmental mechanisms, we analyzed the gene regulatory network (GRN) controlling the development of the apical organ in sea urchins. We characterized the developmental expression of 30 transcription factors and identified key regulatory functions for FoxQ2, Hbn, Delta/Notch signaling, and SoxC in the patterning of the apical organ and the specification of neurons. Almost the entire set of apical transcription factors is expressed in the nervous system of worms, flies, zebrafish, frogs, and mice. Furthermore, a regulatory module controlling the axial patterning of the vertebrate brain is expressed in the ectoderm of sea urchin embryos. We conclude that GRNs controlling the formation of bilaterian nervous systems share a common origin and that the apical GRN likely resembles an ancestral regulatory program.", "doi": "10.1126/sciadv.abo2416", "pmcid": "PMC9629743", "issn": "2375-2548", "publisher": "American Association for the Advancement of Science", "publication": "Science Advances", "publication_date": "2022-11-04", "series_number": "44", "volume": "8", "issue": "44", "pages": "Art. No. eabo2416" }, { "id": "authors:npps6-p6202", "collection": "authors", "collection_id": "npps6-p6202", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190628-103435076", "type": "article", "title": "Ciliary photoreceptors in sea urchin larvae indicate pan-deuterostome cell type conservation", "author": [ { "family_name": "Valencia", "given_name": "Jonathan E.", "clpid": "Valencia-Jonathan-E" }, { "family_name": "Feuda", "given_name": "Roberto", "orcid": "0000-0003-0857-1732", "clpid": "Feuda-Roberto" }, { "family_name": "Mellott", "given_name": "Dan O.", "clpid": "Mellott-Dan-O" }, { "family_name": "Burke", "given_name": "Robert D.", "clpid": "Burke-Robert-D" }, { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" } ], "abstract": "Background. The evolutionary history of cell types provides insights into how morphological and functional complexity arose during animal evolution. Photoreceptor cell types are particularly broadly distributed throughout Bilateria; however, their evolutionary relationship is so far unresolved. Previous studies indicate that ciliary photoreceptors are homologous at least within chordates, and here, we present evidence that a related form of this cell type is also present in echinoderm larvae. \n \nResults. Larvae of the purple sea urchin Strongylocentrotus purpuratus have photoreceptors that are positioned bilaterally in the oral/anterior apical neurogenic ectoderm. Here, we show that these photoreceptors express the transcription factor Rx, which is commonly expressed in ciliary photoreceptors, together with an atypical opsin of the GO family, opsin3.2, which localizes in particular to the cilia on the cell surface of photoreceptors. We show that these ciliary photoreceptors express the neuronal marker synaptotagmin and are located in proximity to pigment cells. Furthermore, we systematically identified additional transcription factors expressed in these larval photoreceptors and found that a majority are orthologous to transcription factors expressed in vertebrate ciliary photoreceptors, including Otx, Six3, Tbx2/3, and Rx. Based on the developmental expression of rx, these photoreceptors derive from the anterior apical neurogenic ectoderm. However, genes typically involved in eye development in bilateria, including pax6, six1/2, eya, and dac, are not expressed in sea urchin larval photoreceptors but are instead co-expressed in the hydropore canal. \n\nConclusions. Based on transcription factor expression, location, and developmental origin, we conclude that the sea urchin larval photoreceptors constitute a cell type that is likely homologous to the ciliary photoreceptors present in chordates.", "doi": "10.1186/s12915-021-01194-y", "pmcid": "PMC8642985", "issn": "1741-7007", "publisher": "Biomed Central", "publication": "BMC Biology", "publication_date": "2021-12-04", "volume": "19", "pages": "Art. No. 257" }, { "id": "authors:mee2q-0e967", "collection": "authors", "collection_id": "mee2q-0e967", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200601-083530200", "type": "book_section", "title": "Preface", "book_title": "Gene Regulatory Networks", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" } ], "contributor": [ { "family_name": "Peter", "given_name": "Isabelle S.", "clpid": "Peter-I-S" } ], "abstract": "Gene regulatory networks (GRNs) offer an unprecedented view on the genomic control of developmental and evolutionary processes. By regulating gene expression, GRNs control the molecular changes in genome activity that drive development and enable evolution. A lot remains to be learned about how GRNs control developmental mechanisms, and this volume provides just a snapshot of a growing field. Many bits and pieces of regulatory circuits have been discovered, or are currently being investigated, in different animals and particularly also in plants. In many developmental contexts, functional analyses of GRNs are starting to illuminate the control systems that generate causality in the developmental process. This volume focuses in particular on developmental systems where decades of research have provided sufficient tools and insights to generate a causal understanding of the underlying GRNs and the evolution thereof. The articles in this collection discuss current insights into how GRNs operate in various contexts in development and evolution, and also address some of the challenges that lie ahead and that will be solved in coming years as research in this scientific area advances.", "doi": "10.1016/s0070-2153(20)30074-0", "isbn": "978-0-12-813180-0", "publisher": "Elsevier", "place_of_publication": "Cambridge, MA", "publication_date": "2020-05-22", "pages": "xiii-xv" }, { "id": "authors:70rb2-8md38", "collection": "authors", "collection_id": "70rb2-8md38", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200519-095532988", "type": "book_section", "title": "The function of architecture and logic in developmental gene regulatory networks", "book_title": "Gene Regulatory Networks", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" } ], "contributor": [ { "family_name": "Peter", "given_name": "Isabelle S.", "clpid": "Peter-I-S" } ], "abstract": "An important contribution of systems biology is the insight that biological systems depend on the function of molecular interactions and not just on individual molecules. System level mechanisms are particularly important in the development of animals and plants which depends not just on transcription factors and signaling molecules, but also on regulatory circuits and gene regulatory networks (GRNs). However, since GRNs consist of transcription factors, it can be challenging to assess the function of regulatory circuits independently of the function of regulatory factors. The comparison of different GRNs offers a way to do so and leads to several observations. First, similar regulatory circuits operate in various developmental contexts and in different species, and frequently, these circuits are associated with similar developmental functions. Second, given regulatory circuits are often used at particular positions within the GRN hierarchy. Third, in some GRNs, regulatory circuits are organized in a particular order in respect to each other. And fourth, the evolution of GRNs occurs not just by co-option of regulatory genes but also by rewiring of regulatory linkages between conserved regulatory genes, indicating that the organization of interactions is important. Thus, even though in most instances the function of regulatory circuits remains to be discovered, it becomes evident that the architecture and logic of GRNs are functionally important for the control of genome activity and for the specification of the body plan.", "doi": "10.1016/bs.ctdb.2020.04.001", "isbn": "978-0-12-813180-0", "publisher": "Elsevier", "place_of_publication": "Cambridge, MA", "publication_date": "2020-05-19", "pages": "267-295" }, { "id": "authors:awmhp-9bf76", "collection": "authors", "collection_id": "awmhp-9bf76", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190610-075133892", "type": "article", "title": "How Does the Regulatory Genome Work?", "author": [ { "family_name": "Istrail", "given_name": "Sorin", "clpid": "Istrail-Sorin" }, { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" } ], "abstract": "The regulatory genome controls genome activity throughout the life of an organism. This requires that complex information processing functions are encoded in, and operated by, the regulatory genome. Although much remains to be learned about how the regulatory genome works, we here discuss two cases where regulatory functions have been experimentally dissected in great detail and at the systems level, and formalized by computational logic models. Both examples derive from the sea urchin embryo, but assess two distinct organizational levels of genomic information processing. The first example shows how the regulatory system of a single gene, endo16, executes logic operations through individual transcription factor binding sites and cis-regulatory modules that control the expression of this gene. The second example shows information processing at the gene regulatory network (GRN) level. The GRN controlling development of the sea urchin endomesoderm has been experimentally explored at an almost complete level. A Boolean logic model of this GRN suggests that the modular logic functions encoded at the single-gene level show compositionality and suffice to account for integrated function at the network level. We discuss these examples both from a biological-experimental point of view and from a computer science-informational point of view, as both illuminate principles of how the regulatory genome works.", "doi": "10.1089/cmb.2019.0097", "pmcid": "PMC6661970", "issn": "1066-5277", "publisher": "Mary Ann Liebert, Inc.", "publication": "Journal of Computational Biology", "publication_date": "2019-07", "series_number": "7", "volume": "26", "issue": "7", "pages": "685-695" }, { "id": "authors:spz9f-hvx63", "collection": "authors", "collection_id": "spz9f-hvx63", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181204-072548701", "type": "article", "title": "Conserved regulatory state expression controlled by divergent developmental gene regulatory networks in echinoids", "author": [ { "family_name": "Erkenbrack", "given_name": "Eric M.", "orcid": "0000-0001-9375-3279", "clpid": "Erkenbrack-Eric-M" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" }, { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" } ], "abstract": "Evolution of the animal body plan is driven by changes in developmental gene regulatory networks (GRNs), but how networks change to control novel developmental phenotypes remains, in most cases, unresolved. Here, we address GRN evolution by comparing the endomesoderm GRN in two echinoid sea urchins, Strongylocentrotus purpuratus and Eucidaris tribuloides, with at least 268 million years of independent evolution. We first analyzed the expression of twelve transcription factors and signaling molecules of the S. purpuratus GRN in E. tribuloides embryos, showing that orthologous regulatory genes are expressed in corresponding endomesodermal cell fates in the two species. However, perturbation of regulatory genes revealed that important regulatory circuits of the S. purpuratus GRN are significantly different in E. tribuloides. For example, mesodermal Delta/Notch signaling controls exclusion of alternative cell fates in E. tribuloides but controls mesoderm induction and activation of a positive feedback circuit in S. purpuratus. These results indicate that the architecture of the sea urchin endomesoderm GRN evolved by extensive gain and loss of regulatory interactions between a conserved set of regulatory factors that control endomesodermal cell fate specification.", "doi": "10.1242/dev.167288", "pmcid": "PMC6307887", "issn": "0950-1991", "publisher": "Company of Biologists", "publication": "Development", "publication_date": "2018-12-15", "series_number": "24", "volume": "145", "issue": "24", "pages": "Art. No. dev167288" }, { "id": "authors:2kmrm-21x96", "collection": "authors", "collection_id": "2kmrm-21x96", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181211-101728399", "type": "book_section", "title": "Methods for the experimental and computational analysis of gene regulatory networks in sea urchins", "book_title": "Echinoderms, Part B", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" } ], "contributor": [ { "family_name": "Hamdoun", "given_name": "Amro", "clpid": "Hamdoun-A" }, { "family_name": "Foltz", "given_name": "Kathy R.", "clpid": "Foltz-K-R" } ], "abstract": "The discovery of gene regulatory networks (GRNs) has opened a gate to access the genomic mechanisms controlling development. GRNs are systems of transcriptional regulatory circuits that control the differential specification of cell fates during development by regulating gene expression. The experimental analysis of GRNs involves a collection of methods, each revealing aspects of the overall control process. This review provides an overview of experimental and computational methods that have been successfully applied for solving developmental GRNs in the sea urchin embryo. The key in this approach is to obtain experimental evidence for functional interactions between transcription factors and regulatory DNA. In the second part of this review, a more generally applicable strategy is discussed that shows a path from experimental evidence to annotation of regulatory linkages to the generation of GRN models.", "doi": "10.1016/bs.mcb.2018.10.003", "isbn": "9780128170724", "publisher": "Academic Press", "place_of_publication": "San Diego, CA", "publication_date": "2018-12-11", "pages": "89-113" }, { "id": "authors:94p2w-1mh56", "collection": "authors", "collection_id": "94p2w-1mh56", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170629-151929097", "type": "article", "title": "Regulatory states in the developmental control of gene expression", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" } ], "abstract": "A growing body of evidence shows that gene expression in multicellular organisms is controlled by the combinatorial function of multiple transcription factors. This indicates that not the individual transcription factors or signaling molecules, but the combination of expressed regulatory molecules, the regulatory state, should be viewed as the functional unit in gene regulation. Here, I discuss the concept of the regulatory state and its proposed role in the genome-wide control of gene expression. Recent analyses of regulatory gene expression in sea urchin embryos have been instrumental for solving the genomic control of cell fate specification in this system. Some of the approaches that were used to determine the expression of regulatory states during sea urchin embryogenesis are reviewed. Significant developmental changes in regulatory state expression leading to the distinct specification of cell fates are regulated by gene regulatory network circuits. How these regulatory state transitions are encoded in the genome is illuminated using the sea urchin endoderm\u2013mesoderms cell fate decision circuit as an example. These observations highlight the importance of considering developmental gene regulation, and the function of individual transcription factors, in the context of regulatory states.", "doi": "10.1093/bfgp/elx009", "pmcid": "PMC5860005", "issn": "2041-2649", "publisher": "Oxford University Press", "publication": "Briefings in Functional Genomics", "publication_date": "2017-09", "series_number": "5", "volume": "16", "issue": "5", "pages": "281-287" }, { "id": "authors:bxmj5-jjz97", "collection": "authors", "collection_id": "bxmj5-jjz97", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170607-093633287", "type": "article", "title": "Assessing regulatory information in developmental gene regulatory networks", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" } ], "abstract": "Gene regulatory networks (GRNs) provide a transformation function between the static genomic sequence and the primary spatial specification processes operating development. The regulatory information encompassed in developmental GRNs thus goes far beyond the control of individual genes. We here address regulatory information at different levels of network organization, from single node to subcircuit to large-scale GRNs and discuss how regulatory design features such as network architecture, hierarchical organization, and cis-regulatory logic contribute to the developmental function of network circuits. Using specific subcircuits from the sea urchin endomesoderm GRN, for which both circuit design and biological function have been described, we evaluate by Boolean modeling and in silico perturbations the import of given circuit features on developmental function. The examples include subcircuits encoding positive feedback, mutual repression, and coherent feedforward, as well as signaling interaction circuitry. Within the hierarchy of the endomesoderm GRN, these subcircuits are organized in an intertwined and overlapping manner. Thus, we begin to see how regulatory information encoded at individual nodes is integrated at all levels of network organization to control developmental process.", "doi": "10.1073/pnas.1610616114", "pmcid": "PMC5468647", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2017-06-06", "series_number": "23", "volume": "114", "issue": "23", "pages": "5862-5869" }, { "id": "authors:zjpr0-9cn52", "collection": "authors", "collection_id": "zjpr0-9cn52", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170418-093907798", "type": "article", "title": "Sequential Response to Multiple Developmental Network Circuits Encoded in an Intronic cis- Regulatory Module of Sea Urchin hox11/13b", "author": [ { "family_name": "Cui", "given_name": "Miao", "clpid": "Cui-Miao" }, { "family_name": "Vielmas", "given_name": "Erika", "clpid": "Vielmas-E" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" }, { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" } ], "abstract": "Gene expression in different spatial domains is often controlled by separate cis-regulatory modules (CRMs), but regulatory states determining CRM activity are not only distinct in space, they also change continuously during developmental time. Here, we systematically analyzed the regulatory sequences controlling hox11/13b expression and identified a single CRM required throughout embryonic gut development. We show that within this CRM, distinct sets of binding sites recognizing Ets, Tcf, and homeodomain transcription factors control the dynamic spatial expression of hox11/13b in each developmental phase. Several binding sites execute multiple, sometimes contradictory, regulatory functions, depending on the temporal and spatial regulatory context. In addition, we identified a nearby second CRM operating in inter-modular AND logic with the first CRM to control hox11/13b expression in hindgut endoderm. Our results suggest a mechanism for continuous gene expression in response to changing developmental network functions that depends on sequential combinatorial regulation of individual CRMs.", "doi": "10.1016/j.celrep.2017.03.039", "issn": "2211-1247", "publisher": "Elsevier", "publication": "Cell Reports", "publication_date": "2017-04-11", "series_number": "2", "volume": "19", "issue": "2", "pages": "364-374" }, { "id": "authors:twfsm-75782", "collection": "authors", "collection_id": "twfsm-75782", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170711-123728168", "type": "book_section", "title": "A View on Systems Biology Beyond Scale and Method", "book_title": "Philosophy of Systems Biology: Perspectives from Scientists and Philosophers", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" } ], "contributor": [ { "family_name": "Green", "given_name": "Sara", "clpid": "Green-S" } ], "abstract": "\"In times when we are flooded with information, in biology and elsewhere, it might be more important than ever to reflect upon the ways by which we acquire and organize information in order to expand current knowledge. Long decades of scientific research have produced so many thoughts and concepts and open questions, many of which can only now be adequately addressed, with the techniques to acquire large scale experimental data at many different levels of biological organization, from nucleic acid to morphology. How current insights can be used to generate a framework concept, and how such framework plus current technology can be used to access what is not yet known is not just of philosophical concern, but of crucial importance for the ability of systems biology approaches to contribute to the solution of some of the long-standing questions in biology, and to formulate new ideas and concepts.\"", "doi": "10.1007/978-3-319-47000-9_22", "isbn": "978-3-319-46999-7", "publisher": "Springer", "place_of_publication": "Cham, Switzerland", "publication_date": "2016-12-16", "pages": "237-245" }, { "id": "authors:vkx5e-hpr54", "collection": "authors", "collection_id": "vkx5e-hpr54", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160201-141331521", "type": "article", "title": "Eric Davidson. A genomic control odyssey", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" } ], "abstract": "While writing this article, I came to realize that it is utterly impossible to capture the spirit, scientific contributions, or colorful personality of Eric Davidson in a few pages, or even a whole journal, and so I won't even try. I would nevertheless like to pay tribute to an enormously powerful mind and a great intellectual partner and friend, with whom I worked very closely over the last almost nine years, and I will do so in two ways. On the one hand, I will give a brief and entirely subjective account of what I would regard as the most profound expression of his scientific intellect, which is his lifelong journey to understand the genomic control of development. On the other hand, I will remember Eric's very expressive personality in the form of but a few examples of our interactions. What impressed me most about Eric's spirit, of which I am reminded by the photograph in Fig. 1, is that despite the incredible amount of his achievements, Eric never stopped until his very last day to think about what lays ahead, driven by immense curiosity and a deep desire to understand the natural world around us.", "doi": "10.1016/j.ydbio.2016.01.027", "issn": "0012-1606", "publisher": "Elsevier", "publication": "Developmental Biology", "publication_date": "2016-04-15", "series_number": "2", "volume": "412", "issue": "2", "pages": "S41-S44" }, { "id": "authors:ens6b-2nd36", "collection": "authors", "collection_id": "ens6b-2nd36", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160321-080226935", "type": "book_section", "title": "Implications of Developmental Gene Regulatory Networks Inside and Outside Developmental Biology", "book_title": "Essays on Developmental Biology", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" } ], "contributor": [ { "family_name": "Wassarman", "given_name": "Paul M.", "clpid": "Wassarman-P-M" } ], "abstract": "The insight that the genomic control of developmental process is encoded in the form of gene regulatory networks has profound impacts on many areas of modern bioscience. Most importantly, it affects developmental biology itself, as it means that a causal understanding of development requires knowledge of the architecture of regulatory network interactions. Furthermore, it follows that functional changes in developmental gene regulatory networks have to be considered as a primary mechanism for evolutionary process. We here discuss some of the recent advances in gene regulatory network biology and how they have affected our current understanding of development, evolution, and regulatory genomics.", "doi": "10.1016/bs.ctdb.2015.12.014", "isbn": "9780128013823", "publisher": "Academic Press", "place_of_publication": "Cambridge, Mass.", "publication_date": "2016", "pages": "237-251" }, { "id": "authors:6pk6h-3v814", "collection": "authors", "collection_id": "6pk6h-3v814", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20151001-085324137", "type": "book", "title": "Genomic Control Process: Development and Evolution", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" } ], "abstract": "In our time, the sheer volume of published experimental measurements, their scope and technical sophistication, compounded with a proliferation of diverse approaches, objectives, and model systems, has made it particularly difficult to see the conceptual forest for the trees. Yet all of the elegant and sophisticated though disparate and unconnected data sets with which we are confronted represent biological output of the same fundamental operating principles. Each experimental system provides a different window which offers a pathway to these principles. In this book we provide a conceptual framework that we hope will make accessible the principles by which the genomic control system operates developmental and evolutionary process. This framework grows from the realization that the most fundamental causal principles in biology, which distinguish biology from all other sciences, emerge from the existence and function of genomic information. From the genomic sequence are to be recovered the determinants of body plan development in animals. Of course, the processes of biology are subject to the same laws of physics and chemistry as are those of the inanimate world, but it is the genome that mandates biological organization. This is not a metaphor, it is a description of mechanisms that we can now begin to perceive as an unbroken chain of causal connections, leading from the A's, C's, G's and T's of the genomic DNA to the developmental formulation of the elements of the organism.\n\nThe new field that is coalescing around the concepts of genomic information processing partakes of principles and evidence from systems biology, developmental molecular biology, various aspects of body plan evolution and phylogenetics, as well as biological engineering and computational modeling. We found it useful to select and incorporate insights from all of these fields, where these illuminate the genomic control of development, without operating wholly within the paradigms of any one of them. In this book we focus on the main characteristics of the genomic control system, which include its hierarchy, its logic processing functions and its structural organization in the form of gene regulatory networks. Such networks encompass at a system level the recognition interactions between transcription factors and DNA sequence that lie at the heart of the whole regulatory process. The general operational properties of genomic regulatory systems are shared across the Bilateria, while diversity in animal forms directly reflects diversity in genomic developmental programs. Focus on the genomic programs controlling development provides a single conceptual lens through which the most disparate phenomena of development and evolution can be viewed, causally understood and interpreted.", "isbn": "978-0-12-404729-7", "publisher": "Academic Press", "place_of_publication": "San Diego", "publication_date": "2015" }, { "id": "authors:1se4h-fb726", "collection": "authors", "collection_id": "1se4h-fb726", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141111-151009684", "type": "article", "title": "Specific functions of the Wnt signaling system in gene regulatory networks throughout the early sea urchin embryo", "author": [ { "family_name": "Cui", "given_name": "Miao", "clpid": "Cui-Miao" }, { "family_name": "Siriwon", "given_name": "Natnaree", "clpid": "Siriwon-N" }, { "family_name": "Li", "given_name": "Enhu", "clpid": "Li-Enhu" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" }, { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" } ], "abstract": "Wnt signaling affects cell-fate specification processes throughout embryonic development. Here we take advantage of the well-studied gene regulatory networks (GRNs) that control pregastrular sea urchin embryogenesis to reveal the gene regulatory functions of the entire Wnt-signaling system. Five wnt genes, three frizzled genes, two secreted frizzled-related protein 1 genes, and two Dickkopf genes are expressed in dynamic spatial patterns in the pregastrular embryo of Strongylocentrotus purpuratus. We present a comprehensive analysis of these genes in each embryonic domain. Total functions of the Wnt-signaling system in regulatory gene expression throughout the embryo were studied by use of the Porcupine inhibitor C59, which interferes with zygotic Wnt ligand secretion. Morpholino-mediated knockdown of each expressed Wnt ligand demonstrated that individual Wnt ligands are functionally distinct, despite their partially overlapping spatial expression. They target specific embryonic domains and affect particular regulatory genes. The sum of the effects of blocking expression of individual wnt genes is shown to equal C59 effects. Remarkably, zygotic Wnt-signaling inputs are required for only three general aspects of embryonic specification: the broad activation of endodermal GRNs, the regional specification of the immediately adjacent stripe of ectoderm, and the restriction of the apical neurogenic domain. All Wnt signaling in this pregastrular embryo is short range (and/or autocrine). Furthermore, we show that the transcriptional drivers of wnt genes execute important specification functions in the embryonic domains targeted by the ligands, thus connecting the expression and function of wnt genes by encoded cross-regulatory interactions within the specific regional GRNs.", "doi": "10.1073/pnas.1419141111", "pmcid": "PMC4250154", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2014-11-25", "series_number": "47", "volume": "111", "issue": "47", "pages": "E5029-E5038" }, { "id": "authors:8krj7-gnd46", "collection": "authors", "collection_id": "8krj7-gnd46", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140225-091728610", "type": "article", "title": "Encoding regulatory state boundaries in the pregastrular oral ectoderm of the sea urchin embryo", "author": [ { "family_name": "Li", "given_name": "Enhu", "clpid": "Li-Enhu" }, { "family_name": "Cui", "given_name": "Miao", "clpid": "Cui-Miao" }, { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" } ], "abstract": "By gastrulation the ectodermal territories of the sea urchin embryo have developed an unexpectedly complex spatial pattern of sharply bounded regulatory states, organized orthogonally with respect to the animal/vegetal and oral/aboral axes of the embryo. Although much is known of the gene regulatory network (GRN) linkages that generate these regulatory states, the principles by which the boundaries between them are positioned and maintained have remained undiscovered. Here we determine the encoded genomic logic responsible for the boundaries of the oral aspect of the embryo that separate endoderm from ectoderm and ectoderm from neurogenic apical plate and that delineate the several further subdivisions into which the oral ectoderm per se is partitioned. Comprehensive regulatory state maps, including all spatially expressed oral ectoderm regulatory genes, were established. The circuitry at each boundary deploys specific repressors of regulatory states across the boundary, identified in this work, plus activation by broadly expressed positive regulators. These network linkages are integrated with previously established interactions on the oral/aboral axis to generate a GRN model encompassing the 2D organization of the regulatory state pattern in the pregastrular oral ectoderm of the embryo.", "doi": "10.1073/pnas.1323105111", "pmcid": "PMC3956148", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2014-03-11", "series_number": "10", "volume": "111", "issue": "10", "pages": "E906-E913" }, { "id": "authors:rh36f-pkt87", "collection": "authors", "collection_id": "rh36f-pkt87", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130708-130927897", "type": "article", "title": "A New Software Package for Predictive Gene Regulatory Network Modeling and Redesign", "author": [ { "family_name": "Faure", "given_name": "Emmanuel", "clpid": "Faure-E" }, { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" } ], "abstract": "The efficacy of a newly created software package for predictive modeling of developmental gene regulatory networks (GRNs) has recently been demonstrated (Peter et al., 2012). The program GeNeTool computes spatial gene expression patterns based on GRN interactions and thereby allows the direct comparison of predicted and observed spatial expression patterns. GeNeTool also permits in silico exploration of both cis- and trans- perturbations of GRN interactions. Here, we present this program, review briefly its major features and applications, and provide a detailed and accessible tutorial.", "doi": "10.1089/cmb.2012.0297", "pmcid": "PMC3667423", "issn": "1066-5277", "publisher": "Mary Ann Liebert, Inc.", "publication": "Journal of Computational Biology", "publication_date": "2013-05-29", "series_number": "6", "volume": "20", "issue": "6", "pages": "419-423" }, { "id": "authors:963fc-94392", "collection": "authors", "collection_id": "963fc-94392", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120829-075215429", "type": "article", "title": "Predictive computation of genomic logic processing functions in embryonic development", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" }, { "family_name": "Faure", "given_name": "Emmanuel", "clpid": "Faure-E" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" } ], "abstract": "Gene regulatory networks (GRNs) control the dynamic spatial patterns of regulatory gene expression in development. Thus, in principle, GRN models may provide system-level, causal explanations of developmental process. To test this assertion, we have transformed a relatively well-established GRN model into a predictive, dynamic Boolean computational model. This Boolean model computes spatial and temporal gene expression according to the regulatory logic and gene interactions specified in a GRN model for embryonic development in the sea urchin. Additional information input into the model included the progressive embryonic geometry and gene expression kinetics. The resulting model predicted gene expression patterns for a large number of individual regulatory genes each hour up to gastrulation (30 h) in four different spatial domains of the embryo. Direct comparison with experimental observations showed that the model predictively computed these patterns with remarkable spatial and temporal accuracy. In addition, we used this model to carry out in silico perturbations of regulatory functions and of embryonic spatial organization. The model computationally reproduced the altered developmental functions observed experimentally. Two major conclusions are that the starting GRN model contains sufficiently complete regulatory information to permit explanation of a complex developmental process of gene expression solely in terms of genomic regulatory code, and that the Boolean model provides a tool with which to test in silico regulatory circuitry and developmental perturbations.", "doi": "10.1073/pnas.1207852109", "pmcid": "PMC3478651", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2012-10-09", "series_number": "41", "volume": "109", "issue": "41", "pages": "16434-16442" }, { "id": "authors:vrfk6-p3y78", "collection": "authors", "collection_id": "vrfk6-p3y78", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200519-154017901", "type": "book_section", "title": "Pattern Formation in Sea Urchin Endomesoderm as Instructed by Gene Regulatory Network Topologies", "book_title": "Pattern Formation in Morphogenesis: Problems and Mathematical Issues", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" } ], "contributor": [ { "family_name": "Capasso", "given_name": "Vincenzo", "clpid": "Capasso-V" }, { "family_name": "Gromov", "given_name": "Misha", "clpid": "Gromov-M" }, { "family_name": "Harel-Bellan", "given_name": "Annick", "clpid": "Harel-Bellan-A" }, { "family_name": "Morozova", "given_name": "Nadya", "clpid": "Morozova-N" }, { "family_name": "Pritchard", "given_name": "Linda Louise", "clpid": "Pritchard-L-L" } ], "abstract": "Animals consist of body parts which are spatially discrete functional units. The spatial separation of these body parts and the diversification of their function and structure are developmentally controlled by gene regulatory networks. The transcription factors and signaling molecules which participate in the spatial organization of a developing organism are components of these networks. The causal linkages in the network consist of the regulatory interactions of each factor with its target genes. Interactions among different regulatory genes are responsible for forming specific spatial patterns of gene expression. The architecture of these regulatory interactions and how they instruct the formation of specific spatial domains is directly determined by the genomic sequence. In the sea urchin embryo, many such spatial domains are established early in development. A well-characterized gene regulatory network underlies the specification of endodermal and mesodermal regulatory domains in this embryo. We review multiple examples which reveal the causal logic underlying genomic control strategies for pattern formation during sea urchin embryogenesis.", "doi": "10.1007/978-3-642-20164-6_8", "isbn": "978-3-642-20163-9", "publisher": "Springer", "place_of_publication": "Berlin", "publication_date": "2012-08-05", "pages": "75-92" }, { "id": "authors:2hp1f-00j30", "collection": "authors", "collection_id": "2hp1f-00j30", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110912-113932797", "type": "article", "title": "Transphyletic conservation of developmental regulatory state in animal evolution", "author": [ { "family_name": "Royo", "given_name": "Jos\u00e9 Luis", "clpid": "Royo-J-L" }, { "family_name": "Maeso", "given_name": "Ignacio", "clpid": "Maeso-I" }, { "family_name": "Irimia", "given_name": "Manuel", "clpid": "Irimia-M" }, { "family_name": "Gao", "given_name": "Feng", "clpid": "Gao-Feng" }, { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" }, { "family_name": "Lopes", "given_name": "Carla S.", "clpid": "Lopes-C-S" }, { "family_name": "D'Aniello", "given_name": "Salvatore", "clpid": "D'Aniello-S" }, { "family_name": "Casares", "given_name": "Fernando", "clpid": "Casares-F" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" }, { "family_name": "Garcia-Fern\u00e1ndez", "given_name": "Jordi", "clpid": "Garcia-Fern\u00e1ndez-J" }, { "family_name": "G\u00f3mez-Skarmeta", "given_name": "Jos\u00e9 Luis", "clpid": "G\u00f3mez-Skarmeta-J-L" } ], "abstract": "Specific regulatory states, i.e., sets of expressed transcription factors, define the gene expression capabilities of cells in animal development. Here we explore the functional significance of an unprecedented example of regulatory state conservation from the cnidarian Nematostella to Drosophila, sea urchin, fish, and mammals. Our probe is a deeply conserved cis-regulatory DNA module of the SRY-box B2 (soxB2), recognizable at the sequence level across many phyla. Transphyletic cis-regulatory DNA transfer experiments reveal that the plesiomorphic control function of this module may have been to respond to a regulatory state associated with neuronal differentiation. By introducing expression constructs driven by this module from any phyletic source into the genomes of diverse developing animals, we discover that the regulatory state to which it responds is used at different levels of the neurogenic developmental process, including patterning and development of the vertebrate forebrain and neurogenesis in the Drosophila optic lobe and brain. The regulatory state recognized by the conserved DNA sequence may have been redeployed to different levels of the developmental regulatory program during evolution of complex central nervous systems.", "doi": "10.1073/pnas.1109037108", "pmcid": "PMC3161536", "issn": "0027-8424", "publisher": "National Academy of Sciences", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "publication_date": "2011-08-23", "series_number": "34", "volume": "108", "issue": "34", "pages": "14186-14191" }, { "id": "authors:p8hg7-pfj16", "collection": "authors", "collection_id": "p8hg7-pfj16", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110712-093149607", "type": "article", "title": "A gene regulatory network controlling the embryonic specification of endoderm", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" } ], "abstract": "Specification of endoderm is the prerequisite for gut formation in the embryogenesis of bilaterian organisms. Modern lineage labelling studies have shown that in the sea urchin embryo model system, descendants of the veg1 and veg2 cell lineages produce the endoderm, and that the veg2 lineage also gives rise to mesodermal cell types. It is known that Wnt/\u03b2-catenin signalling is required for endoderm specification and Delta/Notch signalling is required for mesoderm specification. Some direct cis-regulatory targets of these signals have been found and various phenomenological patterns of gene expression have been observed in the pre-gastrular endomesoderm. However, no comprehensive, causal explanation of endoderm specification has been conceived for sea urchins, nor for any other deuterostome. Here we propose a model, on the basis of the underlying genomic control system, that provides such an explanation, built at several levels of biological organization. The hardwired core of the control system consists of the cis-regulatory apparatus of endodermal regulatory genes, which determine the relationship between the inputs to which these genes are exposed and their outputs. The architecture of the network circuitry controlling the dynamic process of endoderm specification then explains, at the system level, a sequence of developmental logic operations, which generate the biological process. The control system initiates non-interacting endodermal and mesodermal gene regulatory networks in veg2-derived cells and extinguishes the endodermal gene regulatory network in mesodermal precursors. It also generates a cross-regulatory network that specifies future anterior endoderm in veg2 descendants and institutes a distinct network specifying posterior endoderm in veg1-derived cells. The network model provides an explanatory framework that relates endoderm specification to the genomic regulatory code.", "doi": "10.1038/nature10100", "pmcid": "PMC3976212", "issn": "0028-0836", "publisher": "Nature Publishing Group", "publication": "Nature", "publication_date": "2011-06-30", "series_number": "7353", "volume": "474", "issue": "7353", "pages": "635-639" }, { "id": "authors:md9br-5hv40", "collection": "authors", "collection_id": "md9br-5hv40", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110401-113748264", "type": "article", "title": "Evolution of Gene Regulatory Networks Controlling Body Plan Development", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" } ], "abstract": "Evolutionary change in animal morphology results from alteration of the functional organization of the gene regulatory networks (GRNs) that control development of the body plan. A major mechanism of evolutionary change in GRN structure is alteration of cis-regulatory modules that determine regulatory gene expression. Here we consider the causes and consequences of GRN evolution. Although some GRN subcircuits are of great antiquity, other aspects are highly flexible and thus in any given genome more recent. This mosaic view of the evolution of GRN structure explains major aspects of evolutionary process, such as hierarchical phylogeny and discontinuities of paleontological change.", "doi": "10.1016/j.cell.2011.02.017", "pmcid": "PMC3076009", "issn": "0092-8674", "publisher": "Elsevier", "publication": "Cell", "publication_date": "2011-03-18", "series_number": "6", "volume": "144", "issue": "6", "pages": "970-985" }, { "id": "authors:2mts4-1cn27", "collection": "authors", "collection_id": "2mts4-1cn27", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100513-082606592", "type": "article", "title": "The endoderm gene regulatory network in sea urchin embryos up to mid-blastula stage", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" } ], "abstract": "As the result of early specification processes, sea urchin embryos eventually form various mesodermal cell lineages and a gut consisting of fore-, mid- and hindgut. The progression of specification as well as the overall spatial organization of the organism is encoded in its gene regulatory networks (GRNs). We have analyzed the GRN driving endoderm specification up to the onset of gastrulation and present in this paper the mechanisms which determine this process up to mid-blastula stage. At this stage, the embryo consists of two separate lineages of endoderm precursor cells with distinct regulatory states. One of these lineages, the veg2 cell lineage, gives rise to endoderm and mesoderm cell types. The separation of these cell fates is initiated by the spatially confined activation of the mesoderm GRN superimposed on a generally activated endoderm GRN within veg2 descendants. Here we integrate the architecture of regulatory interactions with the spatial restriction of regulatory gene expression to model the logic control of endoderm development.", "doi": "10.1016/j.ydbio.2009.10.037", "pmcid": "PMC3981691", "issn": "0012-1606", "publisher": "Elsevier", "publication": "Developmental Biology", "publication_date": "2010-04-15", "series_number": "2", "volume": "340", "issue": "2", "pages": "188-199" }, { "id": "authors:bcwcr-dq184", "collection": "authors", "collection_id": "bcwcr-dq184", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20100120-152548304", "type": "article", "title": "Modularity and design principles in the sea urchin embryo gene regulatory network", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" } ], "abstract": "The gene regulatory network (GRN) established experimentally for the pre-gastrular sea urchin embryo provides causal explanations of the biological functions required for spatial specification of embryonic regulatory states. Here we focus on the structure of the GRN which controls the progressive increase in complexity of territorial regulatory states during embryogenesis; and on the types of modular subcircuits of which the GRN is composed. Each of these subcircuit topologies executes a particular operation of spatial information processing. The GRN architecture reflects the particular mode of embryogenesis represented by sea urchin development. Network structure not only specifies the linkages constituting the genomic regulatory code for development, but also indicates the various regulatory requirements of regional developmental processes.", "doi": "10.1016/j.febslet.2009.11.060", "pmcid": "PMC2810318", "issn": "0014-5793", "publisher": "Elsevier", "publication": "FEBS Letters", "publication_date": "2009-12-17", "series_number": "24", "volume": "583", "issue": "24", "pages": "3948-3958" }, { "id": "authors:9dhj2-qfs58", "collection": "authors", "collection_id": "9dhj2-qfs58", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090828-231035403", "type": "article", "title": "Genomic control of patterning", "author": [ { "family_name": "Peter", "given_name": "Isabelle S.", "orcid": "0000-0003-3685-3147", "clpid": "Peter-I-S" }, { "family_name": "Davidson", "given_name": "Eric H.", "clpid": "Davidson-E-H" } ], "abstract": "The development of multicellular organisms involves the partitioning of the organism into territories of cells of specific structure and function. The information for spatial patterning processes is directly encoded in the genome. The genome determines its own usage depending on stage and position, by means of interactions that constitute gene regulatory networks (GRNs). The GRN driving endomesoderm development in sea urchin embryos illustrates different regulatory strategies by which developmental programs are initiated, orchestrated, stabilized or excluded to define the pattern of specified territories in the developing embryo.", "doi": "10.1387/ijdb.072495ip", "pmcid": "PMC3967875", "issn": "0214-6282", "publisher": "University of the Basque Country Press", "publication": "International Journal of Developmental Biology", "publication_date": "2009", "series_number": "5-6", "volume": "53", "issue": "5-6", "pages": "707-716" } ]