| The neural crest is a population of multipotent precursors that are found only in vertebrate embryos. These cells migrate extensively throughout the body and give rise to diverse derivatives, including craniofacial bone and cartilage, melanocytes, and the enteric nervous system. There is a large network of factors involved in neural crest formation, including SoxE factors, Sox9 and Sox10, which are homologous and contain four highly conserved domains. While both are involved in neural crest precursor formation, during neural crest differentiation stages, Sox9 gives rise to facial cartilage while Sox10 gives rise to cranial ganglia and melanocytes. Both of these factors are also involved in inner ear formation, a non-neural crest-derived tissue.; The overall aim of this thesis is to investigate the mechanism by which SoxE factors regulate events in neural crest and inner ear development. The first goal is to investigate if Sox9 and Sox10 are functionally divergent or redundant in the neural crest. In this thesis, experiments performed in Xenopus embryos show that these factors can perform equivalently in both inner ear formation as well as early and late neural crest development.; The second goal of this thesis is to examine how Sox9 and Sox10 can function equivalently but are able to participate in the formation of different cell types within such a close proximity to one another. Experiments here show the presence or absence of the post-translational modification, SUMOylation, is used to dynamically regulate cell fate decisions.; The third goal of this thesis is to uncover the mechanism by which SoxE SUMOylation dynamically regulates cell fate decisions, by examining the role of this post-translational modification on the regulation of the melanocyte-specific promoter, Dct. This thesis shows that the absence of SoxE SUMOylation recruits the co-activator CBP/p300 to the promoter, while the presence of SUMOylation recruits the co-repressor Groucho4 and Pax3. This is potentially a commonly used mechanism throughout development, and not specific to the Dct promoter.; The fourth goal is to provide preliminary evidence on potential SoxE-related projects. Data here shows a novel SoxE phosphorylation site, novel Sox10 interaction partners, and the effects of SoxE domain deletion constructs. |
