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Alternative Title

Role of wnt5b in radial glial proliferation and differentiation during Zebrafish spinal cord development

Publication Date

2017-08-14

First Advisor

Michael J.F. Barresi

Document Type

Masters Thesis

Degree Name

Master of Science

Department

Biological Sciences

Keywords

Zebra danio, Neural stem cells, Cell differentiation, Astrocytes, Neuroglia, Spinal cord-Growth, Wnt genes, Patterning, Zebrafish, Development, Radial glia, Spinal cord, Gfap, Wnt signalling, Wnt5b, Proliferation, Differentiation

Abstract

During embryonic development, the central nervous system is built through the precise balance of neural stem cell proliferation and differentiation. In vertebrate organisms, radial glial cells serve as the resident neural stem cell, giving rise to both neuronal and glial cell types. Secreted morphogenetic factors in the developing neural tube, like those of the wnt pathway, are known to play some of the most important regulatory roles in patterning the diversity of cell differentiation in the spinal cord. However, the complexity of morphogenetic signaling leaves much to be discovered, especially how such potent inducers of proliferation and differentiation are maintained at an appropriate balance for the careful construction of the spinal cord. Here, we are investigating the role of the non-canonical wnt5b signaling protein in radial glial development. We hypothesize that wnt5b protein functions to attenuate the canonical Wnt/β-catenin pathway, which serves to modulate radial glial proliferation. We used both genetic and pharmacological approaches to manipulate wnt5b signaling and the Wnt/β-catenin pathway. We show that loss and gain of wnt5b function results in the increase and decrease of proliferating radial glial cell numbers respectively. These data suggest that wnt5b normally functions to repress radial glial proliferation, which itself may be mediated through the attenuation of Wnt/β-catenin signaling. Ongoing experiments are designed to directly demonstrate that Wnt/β-catenin signaling has the capacity to promote either radial glial proliferation or differentiation depending on the amount of Wnt/β-catenin present, an amount that is in part kept in balance by wnt5b. Lastly, we are employing mathematical modeling of dual antagonistic Wnt secreted morphogens to ensure we are capturing the most critical parameters of Wnt-dependent radial glial development as well as to theoretically determine the most optimal amount of Wnt/β-catenin signaling needed for normal patterns of neuronal and glial differentiation in the spinal cord.

Language

English

Comments

vii, 64 pages : color illustrations. Includes bibliographical references (pages 56-64)

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