Posterior Hox Transcription Factors Drive Multiple Phases of Neural Crest Development
| dc.contributor.advisor | Uribe, Rosa A | en_US |
| dc.creator | Howard, Aubrey Gaylon Adam | en_US |
| dc.date.accessioned | 2023-01-03T21:21:49Z | en_US |
| dc.date.created | 2022-12 | en_US |
| dc.date.issued | 2022-12-02 | en_US |
| dc.date.submitted | December 2022 | en_US |
| dc.date.updated | 2023-01-03T21:21:50Z | en_US |
| dc.description.abstract | In vertebrate embryos, neural crest cells (NCC) as a stem cell population demonstrate a remarkable capacity for both migratory potential as well as a high degree of plasticity. From early embryonic stages, these multipotent cells delaminate from the neural tube, migrate throughout the embryonic body, and differentiate in a wide host of cells lineages, including pigment lineages, corneal endothelium, bone, mesenchyme, glia, and various populations of neurons, such as the enteric nervous system. NCC differentiate into terminal tissues collinear with the anterior-posterior axis, dividing them into four groups: cranial, vagal, trunk, and sacral. Notably, the developmental span of these NCC subpopulations is coincident with the complex and overlapping expression of hox genes, which encode an ancient family of conserved transcription factors. Throughout each of the NCC developmental phases (specification, epithelial-to-mesenchymal transition (EMT), migration, and differentiation), the development of NCC is regulated by a complex and dynamic gene regulatory network, which remains to be full characterized, particularly among the vagal and trunk NCC. Further, the role for more posterior hox transcription factors are here unto unknown within the posterior NCC populations, unlike the cranial NCC. To this end, I have utilized the vertebrate model zebrafish (Danio rerio) to investigate the transcriptional landscape of NCC. I led a team to build and identify an atlas of sox10 cell lineages which includes thousands of transcriptomes from single cells representing stages spanning the lifetime of the fish. Using this transcriptional atlas, I have found a dynamic and diverse set of hox expression codes which define specific NCC and non-NCC lineages in the posterior embryo. Among these codes, hoxb5b was highly enriched and was selected for deeper characterization. Overexpression of hoxb5b revealed that it was sufficient to expand NCC localization domains, but was restricted in its function to early developmental spans. Further, suppression of single and overlapping members of the hox codes identified in the transcriptional atlas demonstrated a requirement for specific hox codes in NCC EMT. Cumulatively these findings support a model in which hox genes participate as potent and required drivers of vagal NCC patterning, expanding our fundamental knowledge of vertebrate development. | en_US |
| dc.embargo.lift | 2023-12-01 | en_US |
| dc.embargo.terms | 2023-12-01 | en_US |
| dc.format.mimetype | application/pdf | en_US |
| dc.identifier.citation | Howard, Aubrey Gaylon Adam. "Posterior Hox Transcription Factors Drive Multiple Phases of Neural Crest Development." (2022) Diss., Rice University. <a href="https://hdl.handle.net/1911/114190">https://hdl.handle.net/1911/114190</a>. | en_US |
| dc.identifier.uri | https://hdl.handle.net/1911/114190 | en_US |
| dc.language.iso | eng | en_US |
| dc.rights | Copyright 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.subject | Neural Crest Cells | en_US |
| dc.subject | Hox | en_US |
| dc.subject | zebrafish | en_US |
| dc.subject | en_US | |
| dc.title | Posterior Hox Transcription Factors Drive Multiple Phases of Neural Crest Development | en_US |
| dc.type | Thesis | en_US |
| dc.type.material | Text | en_US |
| thesis.degree.department | Biochemistry and Cell Biology | en_US |
| thesis.degree.discipline | Natural Sciences | en_US |
| thesis.degree.grantor | Rice University | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | Doctor of Philosophy | en_US |
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