Genetic Analysis of Glial Contribution to Peripheral Nervous System Assembly

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 DESCRIPTION (provided by applicant): Motor nerves play the critical role of shunting information out of the central nervous system to targets in the periphery. Their formation requires the coordinated development of distinct cellular components, including motor axons, the glial cells that ensheath them and surrounding muscle. During nervous system construction, these cells must migrate long distances and coordinate their differentiation, ensuring the efficient propagation of electrical information. In this project, we will investigate the role of perineurial glia in early spinal motor nerve development as well as the role of muscle-nerve interactions during peripheral nerve development and disease. Although spinal motor axons exit the spinal cord in stereotyped positions along the anterior-posterior axis of the vertebrate neural tube and neural crest streams to these locations, the mechanisms that prefigure these exit points are poorly understood. In Aim 1 of this project, we will investigate the hypothesis that perineurial glia and their precursors prefigure motor exit points (MEP) and direct motor axon outgrowth and neural crest migration. In Aim 2, we will investigate the role of dystrophin in early nervous system development in a zebrafish model of Duchenne Muscular Dystrophy (DMD). Coupling genetics and in vivo imaging in the zebrafish, we can: 1) distinctly tease apart facets of motor nerve development, 2) elucidate how they are regulated, 3) lay the groundwork for a more fundamental understanding of the rules that form a functional nervous system and 4) shed light on mechanisms that could be perturbed in disease.