Elucidating the Regulatory Mechanisms that Govern Proneural Gene Function in the Developing Neocortex

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atmire.migration.oldid4528
dc.contributor.advisorSchuurmans, Carol
dc.contributor.authorWilkinson, Grey
dc.contributor.committeememberBerube, Nathalie
dc.contributor.committeememberHansen, David
dc.contributor.committeememberMacDonald, Justin
dc.contributor.committeememberBiernaskie, Jeff
dc.date.accessioned2016-07-15T20:02:07Z
dc.date.available2016-07-15T20:02:07Z
dc.date.issued2016
dc.date.submitted2016en
dc.description.abstractThe neocortex is the site of higher order cognitive functioning and sensory processing. It is an essential region of the brain as a reduction in neocortical mass at birth due to reduced neuronal number is often associated with intellectual deficits and behavioural abnormalities. It is thus important that we decipher how neurogenesis is regulated during neocortical development. My research has focused on determining how neocortical progenitors decide to proliferate or differentiate; a cell fate choice that dictates how many neurons are born during development. Specifically, I have studied the basic helix-loop-helix transcription factors encoded by the proneural genes Neurogenin 2 (Neurog2) and Achaete scute-like 1 (Ascl1). Neurog2 and Ascl1 are expressed in neural progenitor cells and give rise to distinct neuronal and glial cell types. In the developing telencephalon, Neurog2 promotes the differentiation of excitatory projection neurons while Ascl1 promotes the differentiation of interneurons and glioblasts. My general hypothesis was that Neurog2-Ascl1 form a genetic switch, and that the extrinsic/intrinsic cues that control this genetic switch lie at the crux of cortical progenitor cell fate decisions, ensuring that cortical cells differentiate in sequence and on time. Data that supports this hypothesis, demonstrates that Neurog2-Ascl1 do indeed form a cross-repressive genetic switch, acting together to regulate the timing of laminar fate transitions, and conferring a metastable stem cell state onto a subpool of cortical progenitors. Furthermore, I made inroads into understanding how Neurog2 proneural activity is regulated, demonstrating that Mbt1, a polycomb group protein, regulates Neurog2 function. In sum, through my PhD work, I have made significant inroads into deciphering the molecular mechanisms that control the balance between neocortical progenitor cell self-renewal and differentiation.en_US
dc.identifier.citationWilkinson, G. (2016). Elucidating the Regulatory Mechanisms that Govern Proneural Gene Function in the Developing Neocortex (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25867en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/25867
dc.identifier.urihttp://hdl.handle.net/11023/3141
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectBiology--Cell
dc.subjectGenetics
dc.subjectBiology--Molecular
dc.subjectNeuroscience
dc.subjectBiochemistry
dc.subject.classificationDevelopmenten_US
dc.subject.classificationNeocortexen_US
dc.titleElucidating the Regulatory Mechanisms that Govern Proneural Gene Function in the Developing Neocortex
dc.typedoctoral thesis
thesis.degree.disciplineBiochemistry and Molecular Biology
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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