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    Characterization of SOX11 Partner Proteins and Interaction Domains in Xenopus Neurogenesis

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    View/Open: Singleton_georgetown_0076D_14477.pdf (11.MB)

    Creator
    Singleton, Kaela S.
    Advisor
    Silva, Elena M
    ORCID
    https://orcid.org/0000-0003-2610-5890
    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.
    Description
    Ph.D.
    Permanent Link
    http://hdl.handle.net/10822/1060544
    Date Published
    2020
    Subject
    neurogenesis; Sox11; Xenopus; Neurosciences; Neurosciences;
    Type
    thesis
    Embargo Lift Date
    2022-10-19
    Publisher
    Georgetown University
    Extent
    128 leaves
    Collections
    • Graduate Theses and Dissertations - Neuroscience
    Metadata
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    • Cover for Assessing the Function of SOX21 in Xenopus laevis Neurogenesis: Exploring Homeolog Sub-Functionalization

      Assessing the Function of SOX21 in Xenopus laevis Neurogenesis: Exploring Homeolog Sub-Functionalization 

      Damuth, Dillon L (Georgetown University, 2021)
      Neurogenesis is a tightly controlled developmental process through which neural progenitor cells progress to committed neurons. While the SoxB1 transcription factors are well characterized to have functions in the induction ...
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    Georgetown University Seal
    ©2009 - 2022 Georgetown University Library
    37th & O Streets NW
    Washington DC 20057-1174
    202.687.7385
    digitalscholarship@georgetown.edu
    Accessibility