Date of Degree

2-2019

Document Type

Dissertation

Degree Name

Ph.D.

Program

Biology

Advisor

Andreas Kottmann

Committee Members

John Martin

Mark Emerson

Serge Przedborski

Neil Shneider

Subject Categories

Developmental Biology | Developmental Neuroscience | Molecular and Cellular Neuroscience

Keywords

oligodendrocyte, motor neuron, OPC, scaling, floor plate, sonic hedgehog

Abstract

Oligodendrocyte precursor cells (OPCs) arise sequentially first from a ventral and then from a dorsal precursor domain during spinal cord development. Whether the sequential production of OPCs is of physiological significance has not been examined. Here I show that interrupting Sonic hedgehog (Shh) signaling originating from nascent ventricular zone derivatives (VZD), motor neurons and the lateral floor plate, almost completely blocks ventral but not dorsal oligodendrogenesis without noticeably affecting early tissue patterning and embryonic development. In the absence of ventral OPCs, dorsal OPCs increase proliferation and populate the entire spinal cord with increased density. In these mutant mice, dOPCs take on a unique “bushy” morphology and in contrast to their ventral counterparts, do not participate in pruning of excitatory synapses from injured motor neurons. My results reveal a unique ability of ventrally produced OPCs to communicate with post-natal motor neurons and suggests a mechanism by which progressively greater amounts of Shh emanating from nascent motor neurons allows greater numbers of oligodendrocytes to be produced at brachial limb levels compared to thoracic segments.

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