We propose a SNRP at the University of Texas at San Antonio. UTSA is a young institution with a commitment to rapid growth in graduate training and research in Neuroscience, and an emphasis on quantitative and computational research. In the past 3 years the Department of Biology at UTSA has hired 6 promising young tenure-track neurobiology faculty from among the best labs in the country to represent a cross-section of neuroscience disciplines and advance Neuroscience within our institution. Most of these new scientists are assistant professors, who have never previously held faculty positions. In the upcoming 5 years we are committed to hiring 5 additional tenure-track Neuroscientists with research interests in topics fundamental to the understanding of nervous system function and disorders, including neural control of movement, central pattern generation, structural plasticity in the adult nervous system, ion channel structure and function, and behavioral genetics. During this time of rapid growth of our Neuroscience group, we envision the SNRP functioning as the center of the Neuroscience community at UTSA. The program will develop a community of UTSA researchers and their collaborators at other institutions. It will support a shared research infrastructure tailored to Neurobiology research by providing resources and expertise in the design, collection and quantitative analysis of numerical and image data. We will offer training and leadership to foster the development of our promising new faculty. We will provide critical evaluation, advice and support for their collaborative pilot research, by providing guidance and direct help in the administrative and management issues that arise in establishing their new laboratories. The SNRP leadership will also act as an advocate for their interests at the college and university levels as they establish their independent research programs and develop into productive managers, scientists and scholars. A second focus of the SNRP will be to provide training opportunities that supplement the Neurobiology Ph.D program, including seminars, symposia, and year-long competitive training fellowships for students interested in pursuing advanced mathematical or statistical studies while in our program. REVIEW OF INDIVIDUAL PROJECTS AND CORES: Project 1: Origin and regulation of motor neuron identity in hindbrain. Dr. Gary Gaufo and Dr. Anne Moon DESCRIPTION (provided by applicant): The vertebrate hindbrain is essential for controlling an array of behaviors, from voluntary movements of the craniofacial musculature to autonomic functions of the cardiovascular and gastrointestinal systems. These behaviors rely on the precise registration of motor neurons with their peripheral targets along the head and body's anterior-posterior (AP) axis. This highly ordered relationship originates from a simple embryonic body plan in which motor neurons develop within individual rhombomeres and their prospective targets in adjacent branchial arch tissues. A major cellular contribution to this motor neuron-peripheral target relationship;omes from the neural crest cell, a restricted stem cell population that arises from the dorsal rhombomere and migrates into the surrounding branchial arch tissue. The positional information imposed upon the varied cell types constituting this motor neuron circuit is largely provided by the AP-restricted expression of the Hox genes. However, the mechanism that maintains the AP-restricted expression of the Hox genes and their ability to control the differentiation of the neurons derived from the hindbrain and the neural crest cell remain to be defined. In the first aim, we will use a genetic fate map of the rhombomeres to identify the neuronal lineages that arise from neural crest cells and their possible regulation by the Hox genes. In the second aim, we will address the role of Hox genes in neuronal differentiation through the use of a conditional mutagenesis system to disrupt Hox gene function among progenitors and postmitotic motor neurons in the ventral neural tube. In the third aim, we will explore a mechanism by which Fgf signaling regulates motor neuron-subtype identity by repressing the activity of the Hox genes in the hindbrain. The latter aim may reveal a mechanism that establishes the different motor neuron identities along the entire AP axis of the central nervous system. An understanding of the molecular and cellular determinants contributing to the formation of the motor neuron-peripheral target circuit may provide therapeutic insight into damaged nervous tissue and diseases associated with motor neurons and nerve conduction.
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