MOLECULAR CONTROL OF CELL MIGRATION IN THE SPINAL CORD

描述(逐字摘自申请者的摘要)：许多神经科 包括精神分裂症和某些形式的儿童癫痫在内的疾病出现的原因是 这是大脑发育过程中迁移性缺陷的结果。一种具有 已发现影响小鼠大脑中神经元迁移的是 卷轴基因(Reln)。虽然RELN现在已经被克隆和蛋白质(Reelin) 它的编码已经被识别出来，Reelin影响的机制 神经元的迁移仍不清楚。拟议的研究将使用同情 以节前神经元迁移为模型系统研究其功能 Reelin及其信号通路在神经元调控中的作用 迁移。 交感神经节前神经元迁移的分析适用于 Reelin功能对胚胎发育过程中神经元定位影响的研究 原因如下：1)交感神经节前神经元形成离散的 对Reelin有反应的人口。2)节前迁移的持续时间 是短的，路径可以被很好地定义。3)神经节前的迁移 神经元可以进行目前提出的定量分析。 研究。4)迁移的节前神经元可以逆行标记和 在细胞或外植体培养中鉴定，使研究 Reelin信号转导的分子机制。5)诉讼方式 在切片上可以观察Reelin对节前神经元迁移的影响 通过各种摄动实验进行培养，这些实验不能应用于 大脑发育。 拟议的研究将结合2名资深研究人员的专业知识 (T.Curran博士和J.Yip博士)分析了细胞和分子基础 Reelin函数。拟议研究的具体目的是：1)分析 交感神经节前神经元迁移作为模型系统的研究 研究Reelin功能。2)使用节前神经元迁移作为 模型系统，以确定Reelin在神经元迁移中的作用。3) 研究Reelin信号通路在控制黄斑变性中的作用 节前细胞迁移。这些结果将为我们提供关于 Reelin功能的分子和细胞基础，并可能揭示显著的 关于导致毁灭性疾病的机制的信息 异常迁徙。

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.