An Investigation of WNT Function in Radial Glial Neural Progenitor Cells in the Zebrafish Hypothalamus

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Publication Type dissertation
School or College School of Medicine
Department Neurobiology & Anatomy
Author Duncan, Robert Nelson
Title An Investigation of WNT Function in Radial Glial Neural Progenitor Cells in the Zebrafish Hypothalamus
Date 2015-08
Description The mammalian hypothalamus has recently been shown to support the continual generation of new neurons, even in adults. The zebrafish also generates neurons in the adult. I have undertaken a multifaceted investigation into the regulation of the cells that support this homeostatic addition of neurons to the hypothalamus, radial glial cells, by the Wnt/β-Catenin signaling pathway. In Chapter 1, I describe the nature of neural stem cell populations and their development. I go on to describe Wnt signaling pathways and their potential regulation of neurogenesis through mitogenic affects on stem cell populations and promotion of differentiation. In Chapter 2, I present the first comprehensive analysis of the expression of wnt genes in the vertebrate central nervous system. Using three developmental time points, we have discovered that wnt genes are redundantly expressed throughout development. This analysis will shed light on potential drivers of Wnt signaling pathways that could regulate stem cell function, differentiation of neurons or glia, axonal path-finding, as well as tissue morphogenesis during central nervous system development. Although this investigation was carried out in the zebrafish central nervous system in particular, these data could offer insight into drivers of Wnt signaling pathways in the mammalian central nervous system as well. In Chapter 3, I present a large body of work investigating the nature of radial glial progenitor cells during postembryonic homeostasis in the zebrafish hypothalamus. I iv demonstrate that these neural progenitors are multipotent and support the regeneration of themselves as well as dopaminergic neurons. I go on to determine that Wnt/β-Catenin signaling is not necessary for these phenomena. Interestingly, we have also revealed that in fact, Wnt β-Catenin signaling needs to be kept low in radial glial cells to maintain them as multipotent neural progenitors. In Chapter 4, I discuss the roles for Wnt/β-Catenin signaling in the regulation of differentiation and proliferation of this neural progenitor population. I present several avenues for future investigation that would further shed light on the nature of radial glial cell proliferation in the postembryonic hypothalamus, including candidate signaling pathways that are likely to regulate RG activation. I go on to discuss Wnt/β-Catenin signaling inhibition in RGs as a necessity for their maintenance. Finally, I discuss the mechanisms by which Wnt/β-Catenin signaling may be inhibited specifically within the RG population in the hypothalamus.
Type Text
Publisher University of Utah
Subject MESH Neural Stem Cells; Ependymoglial Cells; Neuroglia; Zebrafish; Hypothalamus; Signal Transduction; Wnt Signaling Pathway; Neurogenesis; beta Catenin; Growth Substances; Cell Differentiation; Regeneration; Amino Acid Substitution; Embryonic Stem Cells; Cell Self Renewal
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital version of An Investigation of WNT Function in Radial Glial Neural Progenitor Cells in the Zebrafish Hypothalamus
Rights Management Copyright © Robert Nelson Duncan 2015
Format Medium application/pdf
Format Extent 20,594,312 bytes
Source Original in Marriott Library Special Collections
ARK ark:/87278/s6fz0jq7
Setname ir_etd
Date Created 2016-04-20
Date Modified 2021-05-06
ID 197355
Reference URL
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