Vertebrate locomotive behavior, such as swimming or walking, requires the precise formation of neural networks within the spinal cord. Although the broad organization of these spinal cord networks is understood, little is known about how these networks are first established and then modified during embryogenesis to produce a mature spinal cord network. This proposal requests a mentored "Career Development Award to Promote Diversity in Neuroscience Research" (K01) to investigate spinal cord network formation in the zebrafish embryo. The applicant is Gerald B. Downes, Ph.D., a recently appointed Assistant Professor in the Biology Department at the University of Massachusetts Amherst. This award will enable Dr. Downes to acquire expertise in microscopic imaging of spinal cord neuron activity in vivo. This powerful technique will complement his existing expertise in genetics and molecular biology, and will allow for a multifaceted approach to examine spinal cord development. Thomas Zoeller, Ph.D. and Peter Hepler, Ph.D., a well-established developmental neurobiologist and live-cell imaging physiologist respectively, will serve as the mentor and co-mentor. Combined, they have substantial experience in developmental neurobiology, imaging cellular activity and mentoring, and will greatly facilitate Dr. Downes'long-term career goal to establish a competitively funded research program. The central research goal for this proposal is to identify genes and cellular events required for the development of spinal cord networks. The experiments in this proposal utilize two members of the accordion class of zebrafish mutants, bajan and squeezebox. These mutants demonstrate aberrant locomotive behavior, consistent with them harboring spinal cord network defects. Neither the mutated gene nor the cellular defect is known in either mutant;therefore they can be effective tools to elucidate the potentially novel genes and cellular events essential for spinal cord network development. Since spinal cord organization is broadly conserved among vertebrates, these studies may provide insight into human spinal cord development. The experiments in this proposal will: 1) test the hypothesis that the bajan and squeezebox genes contribute to spinal cord network formation using imaging approaches;2) resolve the development of abnormal locomotive behavior in each mutant;and 3) determine the molecular identity of both the bajan and squeezebox genes.
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