Investigation of Enteric Neural Crest Cell Differentiation, Proliferation Dynamics and Hirschsprung Disease Manifestation During Zebrafish Enteric Nervous System Development

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dc.contributor.advisorUribe, Rosa Aen_US
dc.contributor.advisorWagner, Dan Sen_US
dc.creatorBaker, Phillip Austinen_US
dc.date.accessioned2022-09-26T19:18:11Zen_US
dc.date.available2022-09-26T19:18:11Zen_US
dc.date.created2022-05en_US
dc.date.issued2022-04-22en_US
dc.date.submittedMay 2022en_US
dc.date.updated2022-09-26T19:18:11Zen_US
dc.description.abstractThe enteric nervous system (ENS) is a vast intrinsic network of neurons and glia within the gastrointestinal tract that is largely derived from enteric neural crest cells (ENCCs) that emigrate into the gut during vertebrate embryonic development. Study of ENCC migration dynamics and their genetic regulators provides great insights into fundamentals of collective cell migration and nervous system formation and are a pertinent subject for study due to their relevance to the human congenital disease, Hirschsprung disease (HSCR). To accomplish these studies contained within my thesis, I used the zebrafish model to investigate early enteric nervous system development in its endogenous context. My first study set out to bridge our gap in understanding between zebrafish and mammalian enteric nervous system cell diversity and structure. For this investigation, I utilized immunohistochemical detection of axonal and glial cell profiles in the larval gut to reveal novel details about zebrafish ENS architecture and maturation. Specifically, I observed that the zebrafish larval enteric plexus is histologically distinct by 7 dpf and contains axon and glial cell profiles that encircle the intestinal epithelium, the details of which had yet to be described in zebrafish. My second study profiling the transcriptomes of migratory ENCCs uncovered evolutionarily conserved and novel transcriptional signatures of differentiating enteric neuron cell types, thereby expanding our knowledge of ENS development. I further detected the presence of opioid receptor transcripts within the ENS at 68–70 hpf, a time when immature enteric neurons are continuing to migrate and pattern within the developing embryo. This discovery of opioid transcripts, oprl1 and oprd1b in migrating enteric neuroblasts, represents the earliest stage in which they have been shown to be expressed within the early developing ENS. Lastly, my final study in which I performed in toto imaging of ENS development in heterozygotic deficient ret mutant zebrafish led to novel findings pertaining to ENCC migration and proliferation dynamics in a Hirschsprung Disease relevant context. Specifically, I discovered proliferation dependent migration behaviors downstream of Ret. These findings suggest that Ret signaling may function to regulate maintenance of a stem-state in enteric neural progenitors.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationBaker, Phillip Austin. "Investigation of Enteric Neural Crest Cell Differentiation, Proliferation Dynamics and Hirschsprung Disease Manifestation During Zebrafish Enteric Nervous System Development." (2022) Diss., Rice University. <a href="https://hdl.handle.net/1911/113387">https://hdl.handle.net/1911/113387</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/113387en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectENS Enteric Nervous Systemen_US
dc.subjectENCC Enteric Neural Crest Cellen_US
dc.subjectNCC Neural Crest Cellen_US
dc.subjectHSCR Hirschsprung Diseaseen_US
dc.subjectIPAN Intrinsic Primary Afferenten_US
dc.subjectNeuron GI Gastrointestinalen_US
dc.subjectCNS Central Nervous Systemen_US
dc.subjectDpf Days post fertilizationen_US
dc.subjectHpf Hours post fertilizationen_US
dc.subjectRTK Receptor Tyrosine Kinaseen_US
dc.subjectGDNF Glial Derived Neurotrophicen_US
dc.subjectFactor PC Principal Componenten_US
dc.subjectGFR GDNF Family of Receptorsen_US
dc.subjectMEN2 Multiple Endocrine Neoplasia 2en_US
dc.subjectPTC Papillary Thyroid Carcinomaen_US
dc.subjectNSCLC Non-small Cell Lung Canceren_US
dc.subjectLOF Loss-of-Functionen_US
dc.subjectNCE Non-Coding Elementsen_US
dc.subjectBP Base Pairen_US
dc.subjectgDNA Genomic DNAen_US
dc.subjectsgRNA short-guide RNAen_US
dc.subjecten_US
dc.titleInvestigation of Enteric Neural Crest Cell Differentiation, Proliferation Dynamics and Hirschsprung Disease Manifestation During Zebrafish Enteric Nervous System Developmenten_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBiochemistry and Cell Biologyen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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