All metazoan organisms must reproduce and defend themselves in order to survive as individuals and as a species. These innate behaviors are so crucial that they are \"hard-wired\" into the brain during the animal\u2019s development. They are also released primarily by the olfactory stimuli detected by the AOB, which synapses into the MEA. The MEA in turn projects to the medial hypothalamic behavior control column, which contains a series of nuclei orchestrating either reproductive or defensive behaviors. These amygdalar-hypothalamic projections are topographically organized, and the sub-circuitries controlling reproduction and defense are segregated both functionally and anatomically.
\r\n\r\nThe topographically organized projections suggest that these neural pathways for reproduction and defense are likely genetically determined, but genes that might control their wiring have not yet been identified. Such a parallel circuit organization with very few cross-talks between the two sub-circuits also poses the problem of how rapid decisions between competing reproductive and defensive behaviors are made by organisms faced with conflicting cues.
\r\n\r\nUsing oligonucleotide microarrays and laser-capture microdissection, I identified that several LIM homeodomain transcription factors mark different regions of the MEA involved in either reproductive or defensive behaviors. I have characterized the projections of these neurons to the hypothalamus, using both genetically encoded anterograde and traditional retrograde tracers. I have also carried out behavioral experiments to assess their differential activations by reproductive and defensive stimuli.
\r\n\r\nMy results indicate that Lhx6 delineates a reproductive pathway, which involves neurons in both MEApd and BSTpr, and their projections to the three reproductive nuclei in the hypothalamic medial behavioral control column (MPN, VMHvl and PMv). Further analysis reveals, counter-intuitively, that VMHvl receives inhibitory projections from this reproductive pathway, and a convergent excitatory projection from neurons in MEApv that are activated by a predator odor. The results suggest that this point-of-convergence may serve to \"gate\" the expression of reproductive behavior, under conditions where animals are exposed to threatening stimuli. Thus, my data identifies a potential neural substrate within the hypothalamus for controlling behavioral decisions in the face of conflicting cues and a transcription factor family that may contribute to the development of this substrate.
", "doi": "10.7907/w6ht-9m14", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:1975", "collection": "thesis", "collection_id": "1975", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05232005-173743", "primary_object_url": { "basename": "Thesis_DS.pdf", "content": "final", "filesize": 20102432, "license": "other", "mime_type": "application/pdf", "url": "/1975/7/Thesis_DS.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Identification and Characterization of Endothelial Specific Genes", "author": [ { "family_name": "Shin", "given_name": "Donghun", "orcid": "0000-0002-7975-9014", "clpid": "Shin-Donghun" } ], "thesis_advisor": [ { "family_name": "Anderson", "given_name": "David J.", "clpid": "Anderson-D-J" } ], "thesis_committee": [ { "family_name": "Alberola-Ila", "given_name": "Jose", "clpid": "Alberola-Ila-J" }, { "family_name": "Anderson", "given_name": "David J.", "clpid": "Anderson-D-J" }, { "family_name": "Zinn", "given_name": "Kai George", "clpid": "Zinn-K-G" }, { "family_name": "Sternberg", "given_name": "Paul W.", "clpid": "Sternberg-P-W" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "Cardiovascular development and its proper function are essential for the development and survival of animals, while malformation of vasculature leads to a variety of diseases. The significance of vasculature during development and in adulthood has been delineated by investigating the functions of genes expressed in the vasculature. Endothelial cells lining the lumen of vessel tubes with a single layer, had long been considered inert, homogeneous cells. However, molecular and genetic studies have provided numerous pieces of evidence, which indicate that endothelial cells are active, dynamic, heterogeneous cells. Among these studies, molecular differences between arterial and venous endothelial cells were first revealed by the observation that ephrin-B2 and its cognate receptor EphB4 are restrictively expressed in arterial and venous endothelial cells, respectively. These genes are not only molecular markers of arteries and veins, but they also play essential roles in cardiovascular development.
\r\n\r\nTo investigate whether the molecular difference between arteries and veins persists into adulthood, I analyzed ephrin-B2 expression in adult tissues including pathological settings. These data indicate that the molecular distinction is maintained in adults, and ephrin-B2 further distinguishes arterial smooth muscle cells from venous smooth muscle cells in adults.
\r\n\r\nEphrin-B2 was serendipitously identified as an arterial marker; therefore, I performed a systematic screen to isolate novel arterial- and venous-specific genes, whose identification and characterization might improve current understanding of vascular biology. Through this screen, I isolated several novel arterial-restricted genes, and one of these genes, Depp (decidual protein induced by progesterone), was characterized in detail by generating a knockout of the Depp locus. Although the homozygous mutant mice appear phenotypically normal, the detailed analysis of Depp expression reveals the heterogeneity of arterial endothelial cells from the early stage of vascular development.
\r\n\r\nI identified another novel gene, D1.1, through the screen; however, D1.1 is expressed in both arterial and venous endothelial cells. The fact that D1.1 is specifically expressed in endothelial cells and encodes a predicted transmembrane protein, prompted me to characterize D1.1 in detail using a tau-LacZ knock-in to the D1.1 locus. The data from the expression analysis suggest D1.1 as a novel marker of adult neovasculature. In addition, the data using a soluble D1.1-Fc fusion protein in several different acute assays suggest that D1.1 may play a functional role in angiogenesis that is compensated in vivo by other, structurally distinct proteins.
", "doi": "10.7907/XV0S-9D71", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:3939", "collection": "thesis", "collection_id": "3939", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-10062004-073848", "primary_object_url": { "basename": "SDBarbeeThesis.pdf", "content": "final", "filesize": 12729386, "license": "other", "mime_type": "application/pdf", "url": "/3939/1/SDBarbeeThesis.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "The Functions of Phosphatidylinositol 3-Kinase in T Lymphocyte Development: Roles in Positive Selection and Thymic Exit", "author": [ { "family_name": "Barbee", "given_name": "Susannah Dale", "clpid": "Barbee-Susannah-Dale" } ], "thesis_advisor": [ { "family_name": "Alberola-Ila", "given_name": "Jose", "clpid": "Alberola-Ila-J" } ], "thesis_committee": [ { "family_name": "Rothenberg", "given_name": "Ellen V.", "clpid": "Rothenberg-E-V" }, { "family_name": "Alberola-Ila", "given_name": "Jose", "clpid": "Alberola-Ila-J" }, { "family_name": "Baltimore", "given_name": "David L.", "clpid": "Baltimore-D-L" }, { "family_name": "Bjorkman", "given_name": "Pamela J.", "clpid": "Bjorkman-P-J" }, { "family_name": "Sternberg", "given_name": "Paul W.", "clpid": "Sternberg-P-W" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "Phosphatidylinositol 3-kinase (PI3K) is an important regulator of cell survival, proliferation, activation, and migration in multiple organisms and cell types. We have sought to determine how PI3K may regulate T lymphocyte development, a process that entails exquisitely coordinated phases of proliferation, differentiation, and intra-organ movement. We have generated transgenic mice that express a PI3K gain-of-function mutant specifically in thymocytes. The p110ABD transgene constitutes the adaptor binding domain of the PI3K catalytic subunit and this fragment associates with adaptor subunits in vivo. p110ABD expression induces constitutive PI3K function, as assessed by the activity of the downstream effector Akt. Furthermore, p110ABD-induced PI3K function potentiates Ca ++ influx induced by sub-optimal crosslinking of the antigen receptor (TCR) on immature thymocytes. Enhancing PI3K activity in developing T cells results in the specific accumulation of late-stage, mature HSA lo CD3hi thymocytes of both lineages. The increased numbers of mature thymocytes can be partly attributed to an improvement in positive selection. This is demonstrated by the ability of p110ABD to promote efficient positive selection of transgenic AND TCR thymocytes in a background that mediates sub-optimal differentiation. The improvement in selection is not biased to the CD4 lineage, since CD4 lineage development is not specifically improved in class I-restricted transgenic TCR animals expressing p110ABD. Furthermore, the effect is specific to positive selection since immature thymocyte survival and negative selection are unaffected by p110ABD expression. The increased mature populations are also partly the result of impaired thymocyte emigration. p110ABD T cells colonize the periphery of neonatal animals and irradiated recipients slower than do non-transgenic T cells. The ability of PI3K to regulate positive selection effect is probably due to enhancement of Itk-mediated Ca++ influx. By contrast, the role of PI3K in emigration appears to be independent of known chemotactic or adhesive factors and may instead reflect the importance of subcellular organization for chemokine receptor signaling.", "doi": "10.7907/3bbr-b515", "publication_date": "2005", "thesis_type": "phd", "thesis_year": "2005" }, { "id": "thesis:2432", "collection": "thesis", "collection_id": "2432", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-06042004-000641", "primary_object_url": { "basename": "toc.pdf", "content": "final", "filesize": 497668, "license": "other", "mime_type": "application/pdf", "url": "/2432/7/toc.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Towards Engineering Immunity", "author": [ { "family_name": "Yang", "given_name": "Lili", "clpid": "Yang-Lili" } ], "thesis_advisor": [ { "family_name": "Baltimore", "given_name": "David L.", "clpid": "Baltimore-D-L" } ], "thesis_committee": [ { "family_name": "Rothenberg", "given_name": "Ellen V.", "clpid": "Rothenberg-E-V" }, { "family_name": "Baltimore", "given_name": "David L.", "clpid": "Baltimore-D-L" }, { "family_name": "Alberola-Ila", "given_name": "Jose", "clpid": "Alberola-Ila-J" }, { "family_name": "Bjorkman", "given_name": "Pamela J.", "clpid": "Bjorkman-P-J" }, { "family_name": "Sternberg", "given_name": "Paul W.", "clpid": "Sternberg-P-W" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "The aim of engineering immunity is to harness and engineer the immune system to treat infectious diseases and cancer. Towards this goal, accumulating evidence shows that the immune system can be manipulated to achieve the desired and improved functions. In the context of cancer therapy, many strategies have appeared to utilize the principle of immune defense to safely and effectively target tumor cells for destruction. These strategies fall into two categories: active immunotherapy and passive immunotherapy. Active immunotherapy involves activating the effectors in the host immune system to inhibit cancer cell growth and reject tumors (e.g., cancer vaccination), while passive immunotherapy is a term for directly providing the host with effectors to react against cancer (e.g., adoptive transfer of in vitro expanded antitumor T cells).
\r\n\r\nWe propose a concept of instructive immunotherapy for cancer. This concept is to use a strategy to guide the host in developing in vivo effector cells capable of targeting cancer. This strategy arises from combination of gene therapy, stem cell therapy and immunotherapy to program hematopoietic stem cells (HSCs) to develop into lymphocytes with desired antitumor specificity. Therefore, taking advantage of the longevity and self-renewal of HSCs, life-long supplies of tumor-specific lymphocytes can be generated in vivo, which exceed the current methods of repetitive immunization and adoptive transfer.
\r\n\r\nTo test the feasibility of this approach, I describe in Chapter 2 the procedure of retrovirus-mediated gene transfer of TCR cDNA into RAG1-deficient HSCs. Subsequent transfer of these genetic modified HSCs into RAG1-deficient mice allows the long-term production of functional antigen-specific T cells.
\r\n\r\nChapter 3 describes a method to impart anti-tumor specificity to the wild-type mouse T cell repertoire. To achieve this, genes encoding a CD8 T cell receptor with the desired anti-tumor specificity were delivered into wild-type HSCs via a retroviral vector. When transferred into host mice, these genetically modified HSCs generated a large population of anti-tumor cytotoxic T cells, accounting for more than 20% of peripheral CD8 T cells. These cells displayed a normal response to antigen stimulation and had the ability to generate and maintain long-term memory. Significant tumor rejection was observed in mice containing these T cells, demonstrating feasibility of instructive cancer immunotherapy.
\r\n\r\nIn recognition of the important roles of helper T cells in anti-tumor immunity, Chapter 4 elaborates a two-arm model to augment tumor-specific immune responses. In the experiment, the two arms, both anti-tumor CD4- and CD8 T cells, were generated by HSC gene transfer method. The resultant immune system in mice could not only suppress tumor growth, but could also eradicate large, solid and vascularized tumors. Coupled with results described in Chapter 3, we demonstrated the great potential of instructive cancer immunotherapy and expanded the scope of engineering immunity.
\r\n\r\nSuccessful immunotherapy relies on understanding the molecular mechanisms that control immune responses. For instance, although IL-2 has been approved by FDA to treat renal cancer and melanoma, many results from mice show that the physiological role of IL-2 is complex and unpredictable, hindering the design of better strategies, that would maximize the therapeutic impact of IL-2. I address the role of IL-2 in negative regulatory function and T cell memory in last two chapters, both of which are important for achieve the overall success of immunotherapy and engineering immunity. Chapter 5 describes the role of IL-2 in maintaining regulatory T cell homeostasis and self-tolerance, and correlates this role with the signaling molecule STAT5. The final chapter (Chapter 6) details the role of IL-2 in generation of CD4 T cell memory.
", "doi": "10.7907/XTDP-SC35", "publication_date": "2004", "thesis_type": "phd", "thesis_year": "2004" }, { "id": "thesis:1314", "collection": "thesis", "collection_id": "1314", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-04092003-155305", "primary_object_url": { "basename": "Abstract.pdf", "content": "final", "filesize": 9539, "license": "other", "mime_type": "application/pdf", "url": "/1314/1/Abstract.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Glial Cell Development in the Vertebrate Central Nervous System", "author": [ { "family_name": "Zhou", "given_name": "Qiao", "clpid": "Zhou-Qiao" } ], "thesis_advisor": [ { "family_name": "Anderson", "given_name": "David J.", "clpid": "Anderson-D-J" } ], "thesis_committee": [ { "family_name": "Bronner", "given_name": "Marianne E.", "clpid": "Bronner-M-E" }, { "family_name": "Anderson", "given_name": "David J.", "clpid": "Anderson-D-J" }, { "family_name": "Alberola-Ila", "given_name": "Jose", "clpid": "Alberola-Ila-J" }, { "family_name": "Zinn", "given_name": "Kai George", "clpid": "Zinn-K-G" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "Neurons and glial cells are the two most fundamental cell types of the vertebrate central nervous system (CNS). While neurons are directly responsible for information processing via their electrical activities, glial cells play essential supportive roles. For example, oligodendroglia insulates axons, microglia performs immune functions, and astroglia maintains homeostasis of the entire CNS. Malfunction of glial cells causes numerous debilitating diseases directly (such as glial tumors), or indirectly by disrupting the normal functions of neurons that they support (as in multiple sclerosis).
\r\n\r\nDespite their functional importance, relatively little is known about the development of vertebrate CNS glial cells. Focusing on the possibility that members of the basic helix-loop-helix (bHLH) transcription factors may play important roles in the development of vertebrate glial cells, similar to their functions in neurons, I searched for novel bHLH factors expressed in glial cells. A new family of bHLH factors was found and named Olig. Intriguingly, one member of this family, Olig2, is sequentially expressed first in motoneuron progenitors and later in the oligodendroglia. The sequence and expression pattern of Olig2 is highly conserved among different vertebrate species including fish, birds and mammals.
\r\n\r\nTo understand the role of Olig2 in oligodendroglia development, I ectopically expressed Olig2 singly or in combination with other factors in chick embryos. My result suggests that Olig2 can promote oligodendrocyte formation in the absence of neurogenic bHLH factors, which are negative regulators of glial fate. Other groups of researchers reported that in the presence of neurogenic factors, Olig2 promotes motoneuron development instead. Olig2 gene is therefore sufficient to specify the fate of either a neuronal subtype or a glial subtype, together with neurogenic factors.
\r\n\r\nTo further assess whether Olig genes are required for motoneuron and oligodendroglia development, I knocked out both Olig2 and Olig1 genes in mouse. In double null mutants, spinal motoneurons and oligodendroglia precursors from the entire CNS fail to develop, demonstrating that Olig genes are absolutely necessary for the generation of these cell types. Unexpectedly, in the absence of both Olig1 and Olig2, spinal motoneurons are transformed into V2 interneurons whereas oligodendroglial cells are respecified as astroglial cells. These results suggest that Olig genes are not involved in neuron-glia decision, but rather in specifying subtype identities of neuron and glia. Given that motoneurons and oligodendrocytes likely derive from common precursors, the expression of Olig may serve to couple the subtype identities of both neurons and glial cells sequentially generated from the same stem cells.
\r\n\r\nThe series of studies on Olig genes contributed on two areas of neural development. First, they shed important light on the specification of oligodendrocyte and astrocyte, the two major glial types in the vertebrate CNS. Second, they revealed that cell fate determinations of neuron and glia are not two unrelated events as often believed, on the contrary, they are deeply intertwined.
", "doi": "10.7907/SV83-BY17", "publication_date": "2003", "thesis_type": "phd", "thesis_year": "2003" }, { "id": "thesis:6968", "collection": "thesis", "collection_id": "6968", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:04242012-143624169", "primary_object_url": { "basename": "Zirlinger_m_2002.pdf", "content": "final", "filesize": 9432064, "license": "other", "mime_type": "application/pdf", "url": "/6968/1/Zirlinger_m_2002.pdf", "version": "v5.0.0" }, "type": "thesis", "title": "Application of Microarray, Laser Capture and Transgenic Technologies to the Study of Neural Diversity", "author": [ { "family_name": "Zirlinger", "given_name": "Mariela", "clpid": "Zirlinger-Mariela" } ], "thesis_advisor": [ { "family_name": "Anderson", "given_name": "David J.", "orcid": "0000-0001-6175-3872", "clpid": "Anderson-D-J" } ], "thesis_committee": [ { "family_name": "Anderson", "given_name": "David J.", "orcid": "0000-0001-6175-3872", "clpid": "Anderson-D-J" }, { "family_name": "Zinn", "given_name": "Kai George", "orcid": "0000-0002-6706-5605", "clpid": "Zinn-K-G" }, { "family_name": "Lester", "given_name": "Henry A.", "orcid": "0000-0002-5470-5255", "clpid": "Lester-H-A" }, { "family_name": "Alberola-Ila", "given_name": "Jose", "clpid": "Alberola-Ila-J" }, { "family_name": "Schuman", "given_name": "Erin Margaret", "orcid": "0000-0002-7053-1005", "clpid": "Schuman-E-M" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "A major quest in modem neurobiology is to understand how the brain controls behavior. To this end, the convergence of two traditionally separate fields, systems neuroscience and molecular neuroscience, is required. The delineation of brain regions responsible for different behaviors, and in particular, their underlying neural circuits should be accompanied by the appreciation of the molecules that compose such circuits.
\r\n\r\nI have taken two approaches toward unraveling the molecular signatures of specific neural structures.\r\nFirst, I conducted microarray-based RNA expression analyses to search, in a large scale and with no a priori constraints, for differentially expressed gene products in several brain regions, including the amygdala, cerebellum, hippocampus, olfactory bulb and periaqueductal gray. Interestingly, only 0.3% of the genes characterized to date showed restricted expression in distinct brain areas. Further characterization by in situ hybridization was performed for genes enriched in the amygdala, a structure that modulates emotional behavior. Remarkably, this revealed that most region-specific genes possessed expression domains whose limits respected subnuclear boundaries defined by classical cytoarchitectonic criteria.\r\nThese analyses were not only informative about the molecular composition of distinct brain areas, but also\r\nprovided tools to genetically dissect the role of different brain nuclei in specific behaviors.
\r\n\r\nSecond, I have used a genetic strategy to label all cellular derivatives of neural crest precursor cells\r\nexpressing a particular gene, Ngn2. Such lineage tracing study uncovered a segregated cellular subpopulation in the developing peripheral nervous system, which was strongly biased for the generation of sensory rather than autonomic neurons. Despite this fate bias, Ngn2-derived cells in the dorsal root ganglion were equally likely to give rise to neurons or glia. This suggests that some neural crest cells\r\nbecome restricted to sensory or autonomic sub lineages before becoming committed to neuronal or glial\r\nfates. In general, visualization of the behavior of neural progenitors during the formation of the nervous\r\nsystem may further our understanding of the generation of specific neuronal subtypes and, eventually,\r\nneuronal connections that shape the functioning brain.
\r\n\r\nThe combination of strategies here described will enable the characterization of brain regions at the molecular level on a broad, systems-based approach.
\r\n", "doi": "10.7907/c701-pk41", "publication_date": "2002", "thesis_type": "phd", "thesis_year": "2002" }, { "id": "thesis:8120", "collection": "thesis", "collection_id": "8120", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03112014-080307279", "primary_object_url": { "basename": "Chang_c_2001.pdf", "content": "final", "filesize": 54645936, "license": "other", "mime_type": "application/pdf", "url": "/8120/1/Chang_c_2001.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Signal Transduction, Regulation, and Developmental Logic of EGFR Signaling in C. elegans", "author": [ { "family_name": "Chang", "given_name": "Chieh", "clpid": "Chang-Chieh" } ], "thesis_advisor": [ { "family_name": "Sternberg", "given_name": "Paul W.", "orcid": "0000-0002-7699-0173", "clpid": "Sternberg-P-W" } ], "thesis_committee": [ { "family_name": "Sternberg", "given_name": "Paul W.", "orcid": "0000-0002-7699-0173", "clpid": "Sternberg-P-W" }, { "family_name": "Hay", "given_name": "Bruce A.", "orcid": "0000-0002-5486-0482", "clpid": "Hay-B-A" }, { "family_name": "Chan", "given_name": "David C.", "orcid": "0000-0002-0191-2154", "clpid": "Chan-D-C" }, { "family_name": "Alberola-Ila", "given_name": "Jose", "orcid": "0000-0003-2439-553X", "clpid": "Alberola-Ila-J" }, { "family_name": "Aroian", "given_name": "Raffi V.", "orcid": "0000-0002-9741-3834", "clpid": "Aroian-R-V" } ], "local_group": [ { "literal": "div_biol" } ], "abstract": "RTKs-mediated signaling systems and the pathways with which they interact (e.g., those initiated by G protein-mediated signaling) involve a highly cooperative network that sense a large number of cellular inputs and then integrate, amplify, and process this information to orchestrate an appropriate set of cellular responses. The responses include virtually all aspects of cell function, from the most fundamental (proliferation, differentiation) to the most specialized (movement, metabolism, chemosensation). The basic tenets of RTK signaling system seem rather well established. Yet, new pathways and even new molecular players continue to be discovered. Although we believe that many of the essential modules of RTK signaling system are rather well understood, we have relatively little knowledge of the extent of interaction among these modules and their overall quantitative importance.
\r\n\r\nMy research has encompassed the study of both positive and negative signaling by RTKs in C. elegans. I identified the C. elegans S0S-1 gene and showed that it is necessary for multiple RAS-mediated developmental signals. In addition, I demonstrated that there is a SOS-1-independent signaling during RAS-mediated vulval differentiation. By assessing signal outputs from various triple mutants, I have concluded that this SOS-1-independent signaling is not mediated by PTP-2/SHP-2 or the removal of inhibition by GAP-1/ RasGAP and it is not under regulation by SLI-1/Cb1. I speculate that there is either another exchange factor for RASor an as yet unidentified signaling pathway operating during RAS-mediated vulval induction in C. elegans.
\r\n\r\nIn an attempt to uncover the molecular mechanisms of negative regulation of EGFR signaling by SLI-1/Cb1, I and two other colleagues codiscovered that RING finger domain of SLI-1 is partially dispensable for activity. This structure-function analysis shows that there is an ubiquitin protein ligase-independent activity for SLI-1 in regulating EGFR signaling. Further, we identified an inhibitory tyrosine of LET-23/ EGFR requiring sli-1(+)for its effects: removal of this tyrosine closely mimics loss of sli-1 but not loss of other negative regulator function.
\r\n\r\nBy comparative analysis of two RTK pathways with similar signaling mechanisms, I have found that clr-1, a previously identified negative regulator of egl-15 mediated FGFR signaling, is also involved in let-23 EGFR signaling. The success of this approach promises a similar reciprocal test and could potentially extend to the study of other signaling pathways with similar signaling logic.
\r\n\r\nFinally, by correlating the developmental expression of lin-3 EGF to let-23 EGFR signaling activity, I demonstrated the existence of reciprocal EGF signaling in coordinating the morphogenesis of epithelia. This developmental logic of EGF signaling could provide a basis to understand a universal mechanism for organogenesis.
", "doi": "10.7907/9qcj-az06", "publication_date": "2001", "thesis_type": "phd", "thesis_year": "2001" } ]