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Author ORCID Identifier

https://orcid.org/0000-0002-4146-259X

AccessType

Open Access Dissertation

Document Type

dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Molecular and Cellular Biology

Year Degree Awarded

2020

Month Degree Awarded

May

First Advisor

Rolf O. Karlstrom

Second Advisor

Lawrence M. Schwartz

Third Advisor

Alicia Timme-Laragy

Fourth Advisor

R. Craig Albertson

Subject Categories

Life Sciences | Other Cell and Developmental Biology

Abstract

The hypothalamus is the central regulator of a diverse homeostatic processes that are essential for the survival of the animal. Recently, the hypothalamus has been shown to be a neurogenic zone in many animal species including mice, zebrafish, sheep and potentially even humans with hypothalamic neurogenesis implicated in energy metabolism, stress, anxiety and reproduction. However, the identification of the cellular components and the signaling mechanisms regulating hypothalamic neurogenesis are only beginning to be elucidated. My dissertation research elucidates the role of Hh signaling in regulating hypothalamic neurogenesis throughout life. The first chapter of the dissertation offers a survey into the field of neurogenesis with a focus on up-to-date information about hypothalamic neurogenesis. Chapter two demonstrates the role of Hh signaling in the ventral forebrain proliferation. More specifically, we reveal for the first time, that Hh signaling is necessary and sufficient for regulating hypothalamic proliferation rates throughout life. Additionally, we show Hh-responsive radial glia as multipotent neural progenitors giving rise to dopaminergic, GABA-ergic and serotonergic neuronal lineages with Hh signaling being both necessary and sufficient for regulating larval serotonergic cell numbers. Chapter three of my dissertation focuses on a detailed description of the proliferative rates of five progenitor cell types present at the hypothalamic lateral (LR) and posterior (PR) recesses. We show that approximately, 60% of Hh-responsive cells in the PR were PCNA positive compared to approximately 20% of Notch-responsive cells and 10% of Shh-producing cells and no proliferative Wnt-responsive. These analyses reveal striking differences in the proliferative profiles among radial glia in the posterior recess with Hh-responsive cells representing a much more proliferative population that may account for the majority of hypothalamic growth in the larval stages. Lastly, chapter four of the dissertation offers a synthesis of the hypothalamic neurogenesis with a focus on the heterogeneity of the neural progenitor types on this brain region. Taken together, my dissertation work reveals a novel role for Hh signaling as a key molecular regulator of hypothalamic proliferation in the zebrafish hypothalamus and provides a foundation for future studies of a mechanism of action.

DOI

https://doi.org/10.7275/17586512

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

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