Characterization of Sox11 in Neurogenesis
CHARACTERIZATION OF SOX11 IN NEUROGENESISJing Jin, B.S.Thesis Advisor: Elena Silva, Ph.D.ABSTRACTDuring neurogenesis, the Sox transcription factors, maintain a balance of proliferating progenitors and differentiating neurons. While a number of studies have demonstrated that SoxB1 proteins maintain a progenitor pool, much less is known about the function and downstream targets of the SoxC proteins. In this work, we studied the expression and functions of the SoxC protein Sox11 during primary neurogenesis in Xenopus laevis. Gain- and loss-of-function analyses support a role for Sox11 promoting neuronal differentiation. Unexpectedly, Sox11 also seems to play a role in controlling the size of the progenitor pool. Using hormone inducible Sox11 and RNA-seq, we found that the dual roles of Sox11 are due to the different functions of maternal and zygotic Sox11: zygotic Sox11 drives neurogenesis, and maternal Sox11 promotes neural progenitors.To determine whether the function of Sox11 is conserved, we compared the function of Sox11 in the Xenopus neural plate and the mouse cerebral cortex. Sox11 is expressed in differentiated neurons in the mouse cortex and gain- and loss-of-function analyses revealed that Sox11 promotes neuronal differentiation, and morphological complexity of axons and dendrites. However, surprisingly, frog and mouse Sox11 cannot substitute for one another; a functional difference likely reflected in sequence divergence. We also investigated how sox11 is post-transcriptionally regulated and discovered the sox11 3’UTR interferes with Sox11 function, and further found it might be due to the interaction between sox11 3’UTR and coding sequence. Future studies will reveal the mechanism.Using computational analysis, we characterized a class of newly identified non-coding RNA: stable intronic sequence RNAs (sisRNAs). It is unclear why the sisRNAs are so unusually stable and whether they have biological functions. We comprehensively examined many aspects of sisRNAs and found sisRNAs are selected intronic regions with distinct properties, supporting sisRNAs have important biological functions.With this report we investigated the functions, downstream targets, conservation, and post-transcriptional regulation of Sox11 in neurogenesis. Our work provides a comprehensive characterization of Sox11 and highlights its importance in neural development. Furthermore, our characterization of sisRNAs provides a foundation for future functional studies.
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Whittington, Niteace Chivon (Georgetown University, 2014)Neurogenesis, the progression from neural progenitor to committed neuron, is a tightly regulated process that is fundamental for development of the central nervous system. Whereas the SoxB1 transcriptional activators are ...