Quantitative Neurobiology at the University of Texas at San Antonio

描述(由申请人提供)：我们建议在圣安东尼奥的德克萨斯大学攻读SNRP。UTSA是一家年轻的机构，致力于神经科学方面的研究生培训和研究的快速增长，并强调定量和计算研究。在过去的三年里，UTSA生物系从全国最好的实验室中聘请了6名有前途的年轻终身教职神经生物学教师，代表神经科学学科的各个领域，并在我们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，我们承诺再招聘5名终身教职神经学家，他们对了解神经系统功能和障碍的基本主题有研究兴趣，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。在我们神经科学集团快速发展的这段时间里，我们设想SNRP将成为UTSA神经科学社区的中心。该计划将建立一个由UTSA研究人员和他们在其他机构的合作者组成的社区。它将通过提供设计、收集和定量分析数字和图像数据的资源和专门知识，支持为神经生物学研究量身定做的共享研究基础设施。我们将提供培训和领导力，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关键的评估、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层面为他们的利益辩护，因为他们建立了独立的研究计划，并发展成为生产性的管理者、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项目的培训机会，包括研讨会、专题讨论会和为期一年的竞争性培训奖学金，供有兴趣在我们项目中进行高级数学或统计研究的学生使用。 对个别项目和核心的审查： 项目1：后脑运动神经元同一性的起源和调控。加里·高福博士和安妮·穆恩博士 描述(申请人提供)：脊椎动物的后脑对于控制一系列行为是必不可少的，从头面部肌肉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与它们的外周目标沿着头部和身体的前后轴(AP)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，在该计划中，运动神经元在单个菱形肌内发育，而它们的预期靶点在相邻的颧弓组织中。对这种运动神经元-外周靶点关系的主要细胞贡献；OMES来自神经脊细胞，这是一种来自背侧菱形核并迁移到周围鳃弓组织的限制性干细胞群体。施加在构成这个运动神经元回路的不同细胞类型上的位置信息很大程度上是由Hox基因的AP限制性表达提供的。然而，维持HOX基因AP-限制性表达的机制以及它们控制来自后脑和神经脊细胞的神经元分化的能力仍有待确定。在第一个目标中，我们将使用菱形核的遗传命运图来确定神经脊细胞产生的神经元谱系以及它们可能受到HOX基因的调控。在第二个目标中，我们将通过使用条件突变系统来破坏腹侧神经管中祖细胞和有丝分裂后运动神经元之间的HOX基因功能，从而探讨HOX基因在神经元分化中的作用。在第三个目标中，我们将探索成纤维细胞生长因子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识别的机制。后一种目的可能揭示一种机制，即沿着中枢神经系统的整个AP轴建立不同的运动神经元身份。对运动神经元-外周靶点回路形成的分子和细胞决定因素的了解可能有助于对受损的神经组织以及与运动神经元和神经传导相关的疾病的治疗洞察。

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.