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Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Molecular and Cellular Biology

Year Degree Awarded

2015

Month Degree Awarded

September

First Advisor

Michael Barresi

Second Advisor

Rolf Karlstrom

Third Advisor

Gerald Downes

Fourth Advisor

Patricia Wadsworth

Subject Categories

Cell and Developmental Biology

Abstract

During embryonic neural development, the concerted actions of neural stem cells (NSCs) populate and pattern the tissues that will give rise to the brain and spinal cord. This heterogeneous NSC population initially consists of neuroepithelial cells, which will generate the first neurons present in the central nervous system (CNS) prior to transitioning into radial glial cells. Classically, radial glial cells are known to play a wide range of roles during CNS development, from maintaining neuronal homeostasis, as a scaffold for neuronal migration, and as a permissive growth substrate for directed axon pathfinding. Recently, radial glial cells have been proposed to also act as a progenitor population for neuronal and glial progenies. Despite their presumed importance, we still lack a foundational understanding of radial glial development and their requirement during development of the central nervous system (CNS). To answer this, I have used genetic and pharmacological approaches to visualize and manipulate radial glial cells throughout embryonic neurogenesis using the zebrafish model system, which maintains radial glia throughout embryonic and adult life. The results of this study demonstrate that radial glia expressing Glial fibrillary acidic protein (Gfap) additionally express NSC markers, are proliferative, and are required to generate late-embryonic neurons and glial cells. This study also provided support for a radial glial requirement in proper neuronal and axon patterning, maintenance of the blood brain barrier, and for a novel role in locomotor behavior. Use of the approaches herein also lead to the identification of a novel, non-radial glial NSC population in the embryonic spinal cord that warrants further study. Taken together, our multifaceted approach supports a role for gfap+ radial glia representing the major neural stem cell during late embryogenesis for specific lineages, and possessing diverse roles to sustain the structure and function of the spinal cord. We predict that these new tools will additionally prove powerful to both exemplify the important roles astroglia are historically suspected in as well as reveal novel roles during development, physiology, and regeneration.

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