The Integration of Multiple Sources of Sonic Hedgehog in the Spinal Cord Contribute to the Production of First-Born Oligodendrocyte Precursor Cells Which Become Critical for Synapse Remodeling in Response to Adult Motor Neuron Injury
Date of Degree
Developmental Biology | Developmental Neuroscience | Molecular and Cellular Neuroscience
oligodendrocyte, motor neuron, OPC, scaling, floor plate, sonic hedgehog
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.
Starikov, Lev, "The Integration of Multiple Sources of Sonic Hedgehog in the Spinal Cord Contribute to the Production of First-Born Oligodendrocyte Precursor Cells Which Become Critical for Synapse Remodeling in Response to Adult Motor Neuron Injury" (2019). CUNY Academic Works.