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The role of capicua in adult hippocampal neurogenesis
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- Author / Creator
- Hourigan, Brenna
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Adult hippocampal neurogenesis (AHN) involves generating hippocampal granule neurons and the subsequent integration of granule neurons into the hippocampus synaptic circuit. This continuous neuron generation supports ongoing learning and memory formation. Consequently, dysregulation of AHN and impairment of synaptic integration have been implicated in various neurological disorders including Alzheimer’s disease, pathological aging, and stress. Thus, by studying the regulation of AHN and how granule neurons are generated, it is possible to identify therapeutic targets which can lead to more effective treatment options for these disorders. To generate functional adult-born neurons, neural progenitor cells proliferate to expand the precursor cell pool and differentiate into neurons. Newly generated cells then undergo postmitotic maturation to migrate to their final destination and develop elaborate dendritic branching, which allows them to receive input signals. Little is known about factors that regulate neuronal differentiation, migration, and dendrite maturation during adult hippocampal neurogenesis. This thesis highlights the importance of the transcriptional repressor capicua (CIC) for AHN. I show that CIC is dynamically expressed within the adult dentate gyrus of the hippocampus, where AHN occurs. The Cre-loxP system was utilized to generate Emx1-Cre; Cicflox/flox mice to remove CIC from forebrain excitatory neurons, including those involved with AHN. By using the Emx1-Cre; Cicflox/flox knockout mice line in combination with immunofluorescence studies, I show that conditionally deleting Cic from the mouse dentate gyrus compromises the adult neural progenitor cell pool without altering their proliferative potential. I further demonstrate that the loss of Cic impedes neuronal lineage development and disrupts dendritic arborization and migration of adult-born neurons. This study uncovers a previously unrecognized role of CIC in neurogenesis of the adult dentate gyrus.
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- Graduation date
- Fall 2023
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- Type of Item
- Thesis
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- Degree
- Master of Science
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- License
- This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.