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Characterizing the hnRNP Q Complex and its Activity in Asymmetric Neural Precursor Cell Divisions during Cerebral Cortex Development

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Title: Characterizing the hnRNP Q Complex and its Activity in Asymmetric Neural Precursor Cell Divisions during Cerebral Cortex Development
Author: Smart, Anastasia
Department: Department of Molecular and Cellular Biology
Program: Molecular and Cellular Biology
Advisor: Vessey, John
Abstract: The development of the cerebral cortex is reliant upon the collaborative efforts of a wide variety of molecular mechanisms, one of which is the ability of neural precursor cells (NPCs) to undergo asymmetric cell division. Asymmetric cell divisions produce two daughter cells with distinct identities, one NPC and one neuron. The identity of each daughter cell is decided by the unequal distribution of cell fate determinants. This imbalance is created by the partitioning of RNA:protein complexes to an intracellular site for localization. As a result, the post-mitotic translation of localized transcripts dictates the relative abundance of cell fate determinants and thus, daughter cell identity. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a family of RNA-binding proteins with diverse functions. This research aimed to characterize the hnRNP Q complex and its activity in asymmetric NPC division. The postnatal expression profile revealed hnRNP Q expression persists beyond embryonic development into the immediate postnatal period. Inhibiting nuclear export in NPCs and isolating the hnRNP Q complex via co-immunoprecipitation indicated hnRNP Q shuttles in and out of the nucleus and is capable of forming nuclear and cytoplasmic complexes, suggesting hnRNP Q is involved in splicing, localization and translational repression. Finally, in vivo knockdown experiments replicated in vitro findings that revealed altered patterns of NPC division that show a bias towards self-renewal.
URI: http://hdl.handle.net/10214/12543
Date: 2018-02-01


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