Characterization of SOX11 Partner Proteins and Interaction Domains in Xenopus Neurogenesis

Abstract

During neurogenesis, transcription factors (TFs) regulate each cellular transition from cell cycle exit, to neuronal differentiation and eventual maturation, ensuring that the correct number and class of neurons are generated. In several neural systems, the Sox TF family are critical to this process. This dissertation describes the molecular mechanism of Sox11, a member of the SoxC TF subfamily, in Xenopus laevis neurogenesis. The first portion focuses on identifying novel Sox11 downstream targets using a hormone inducible version of Sox11 coupled with RNA-sequencing. Our results demonstrate Sox11 has overlapping and stage- specific downstream targets during Xenopus neurogenesis. These targets have roles in a variety of developmental processes, including progenitor cell maintenance and neuron maturation. The second part of this work involves identifying Sox11 partner proteins and mapping the Sox11 interaction domains, using co-immunoprecipitation and Sox11 deletion constructs. Our in vitro studies demonstrate that the pro-neural bHLH TF proteins Neurog2 and the Pou class 3 homeoboc TF Pou3f2 bind to Sox11. However, Xenopus Sox11 does not interact with Neurog1, a driver of neuronal cell fate, in the mouse cerebral cortex. We establish that the N- terminus of Sox11 is necessary for partner protein binding, while the C-terminus is required to promote mature neuron formation. Our data indicate that Sox11 works in a context-dependent manner throughout neurogenesis by partnering with two distinct pro-neural proteins to drive target gene expression and promote neuron formation.