Quantitative Neurobiology at the University of Texas at San Antonio

描述（由申请人提供）：我们建议在德克萨斯大学圣安东尼奥的SNRP。UTSA是一个年轻的机构，致力于神经科学研究生培训和研究的快速增长，并强调定量和计算研究。在过去的3年中，UTSA的生物学系从全国最好的实验室中聘请了6名有前途的年轻终身制神经生物学教师，代表神经科学学科的一个横截面，并在我们的机构内推进神经科学。这些新科学家中的大多数是助理教授，他们以前从未担任过教职。在接下来的5年里，我们致力于聘请5个额外的终身制神经科学家，他们的研究兴趣是理解神经系统功能和疾病的基础，包括运动的神经控制，中枢模式生成，成人神经系统的结构可塑性，离子通道结构和功能，以及行为遗传学。在我们的神经科学组快速增长的这段时间里，我们设想SNRP作为UTSA神经科学社区的中心。该计划将发展UTSA研究人员及其在其他机构的合作者的社区。它将通过提供数字和图像数据的设计，收集和定量分析方面的资源和专业知识，支持为神经生物学研究量身定制的共享研究基础设施。我们将提供培训和领导，以促进我们有前途的新教师的发展。我们将为他们的合作试点研究提供重要的评估，建议和支持，在建立新实验室时出现的行政和管理问题上提供指导和直接帮助。SNRP领导层还将在学院和大学一级为他们的利益辩护，因为他们建立了独立的研究计划，并发展成为富有成效的管理人员，科学家和学者。SNRP的第二个重点将是提供补充神经生物学博士课程的培训机会，包括研讨会，研讨会和为期一年的竞争性培训奖学金，为有兴趣在我们的课程中进行高级数学或统计研究的学生提供。 审查个别项目和核心： 项目1：后脑运动神经元的起源和调控。加里·高福博士和安妮·穆恩博士 描述（由申请人提供）：脊椎动物后脑对于控制一系列行为至关重要，从颅面肌肉组织的自主运动到心血管和胃肠系统的自主功能。这些行为依赖于运动神经元沿着头部和身体的前后（AP）轴与其外周靶沿着的精确配准。这种高度有序的关系起源于一个简单的胚胎体计划，其中运动神经元在单个菱形体内发育，其预期目标在相邻的鳃弓组织中。这种运动神经元-外周靶点关系的主要细胞贡献;来自神经嵴细胞，一种来自背菱形节并迁移到周围鳃弓组织的受限干细胞群。施加在构成该运动神经元电路的不同细胞类型上的位置信息主要由Hox基因的AP限制性表达提供。然而，维持Hox基因的AP限制性表达及其控制来自后脑和神经嵴细胞的神经元分化的能力的机制仍有待确定。在第一个目标中，我们将使用菱体的遗传命运图来识别神经嵴细胞产生的神经元谱系及其可能的Hox基因调控。在第二个目标中，我们将解决Hox基因在神经元分化中的作用，通过使用条件诱变系统来破坏Hox基因在腹侧神经管中的祖细胞和有丝分裂后运动神经元之间的功能。在第三个目标中，我们将探索Fgf信号通过抑制后脑中Hox基因的活性来调节运动神经元亚型身份的机制。后一个目标可能揭示了一种机制，建立不同的运动神经元的身份沿着整个AP轴的中枢神经系统。对运动神经元-外周靶回路形成的分子和细胞决定因素的理解，可以为受损的神经组织和与运动神经元和神经传导相关的疾病提供治疗见解。

DESCRIPTION (provided by applicant): 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.