MOLECULAR CONTROL OF CELL MIGRATION IN THE SPINAL CORD

描述（来自申请人摘要的逐字描述）：许多神经系统疾病 包括精神分裂症和某些形式的儿童癫痫的疾病， 这是大脑发育过程中迁移缺陷的结果一个基因， 被发现影响小鼠脑中神经元迁移的是 reeler基因（reln）。尽管现在已经克隆了RELN， 它编码的基因已经被确定， 神经元迁移仍不清楚。拟议的研究将使用同情 神经节前神经元迁移作为一个模型系统，以研究功能 及其信号通路在神经元调控中的作用 迁移 交感节前神经元迁移的分析是适当的， Reelin蛋白在发育过程中神经元定位功能的研究 原因：1）交感节前神经元形成一个离散的 对瑞琳有反应的人2)节前迁移的持续时间 是短的，并且路径可以被很好地定义。3)节前神经元的迁移 神经元适合于本发明提出的定量分析。 research. 4)迁移的节前神经元可以被逆行标记， 在细胞或外植体培养物中鉴定，使得研究 体外Reelin信号传导的分子机制。5)的作用模式 在切片中可以研究Reelin对节前神经元迁移的影响 通过各种扰动实验培养， 大脑发育 拟定研究将结合2名已确立研究者的专业知识，联合收割机 (Drs. T. Curran和J.Yip）分析了 卷轴功能。本研究的具体目标是：1）分析 交感神经节前神经元迁移作为模型系统， 调查瑞琳的功能2)使用节前神经元迁移作为 模型系统来确定Reelin在神经元迁移中的作用。第三章 研究Reelin信号通路在控制 节前细胞迁移结果将提供重要的见解， 分子和细胞的基础上，Reelin功能，并可能揭示显着 造成毁灭性疾病的机制的资料， 异常迁移

DESCRIPTION (Verbatim from the Applicant's Abstract): Many neurological disorders including schizophrenia and some forms of childhood epilepsy arise as a consequence of migratory defects during brain development. A gene that has been found to influence neuronal migration in the brain of the mouse is the reeler gene (reln). Although reln has now been cloned and the protein (Reelin) that it encodes has been identified, the mechanism by which Reelin affects neuronal migration is still unclear. The proposed studies will use sympathetic preganglionic neuronal migration as a model system to investigate the function of Reelin and the role of its signaling pathway in control of neuronal migration. The analysis of sympathetic preganglionic neuronal migration is appropriate for studies of Reelin function on neuronal positioning during development for a number of reasons: 1) Sympathetic preganglionic neurons form a discrete population that responds to Reelin. 2) The duration of preganglionic migration is short and the pathway can be well defined. 3) The migration of preganglionic neurons is amenable to quantitative analysis as proposed in the present research. 4) Migrating preganglionic neurons can be retrogradely labeled and identified in cell or explant cultures, making it possible to study the molecular mechanisms of Reelin signaling in vitro. 5) The mode of action of Reelin on preganglionic neuronal migration can be investigated in the slice culture through a variety of perturbation experiments that cannot be applied to brain development. Proposed studies will combine the expertise of 2 established investigators (Drs. T. Curran and J. Yip) to analyze the molecular and cellular basis of Reelin function. Specific aims of the proposed research are to: 1) Analyze the migration of sympathetic preganglionic neurons as a model system for investigating Reelin function. 2) Use preganglionic neuronal migration as a model system to determine the role of Reelin in neuronal migration. 3) Investigate the role of the Reelin signaling pathway in control of preganglionic cell migration. Results will provide important insights on the molecular and cellular basis of Reelin function, and may reveal significant information about the mechanisms responsible for devastating diseases caused by abnormal migration.