NEURONAL MIGRATION IN THE DEVELOPING BRAIN

描述(逐字摘自申请者摘要)：在开发 中枢神经系统，在增殖区出生的神经元长时间迁移 到达其最终位置的距离。这一过程是正常的必不可少的 神经系统的发育和功能。神经元迁移障碍 在大脑的异常发育和功能障碍中起因果作用，例如 双皮质综合征和癫痫。大脑皮层神经元产生于 脑室带和脑室下带(SVZ)向外迁移到皮质 沿着胶质纤维板状排列。嗅觉神经元间前体在SVZ中的产生 在前前脑(SVZa)，以“链”的形式迁移到嗅球。 需要神经细胞黏附分子的聚唾液酸部分的工艺 (NCAM)。长期目标是阐明这种分子机制 调节神经元的迁移。工作假说是人类的迁徙 嗅觉神经元前体和大脑皮层神经元被引导， 在一定程度上，是由于一种不明的化学排斥因素。为了检验这一假设， 提出了以下具体目标。具体目标1：分子克隆 通过克隆候选分子GP-190，间隔衍生出趋化排斥因子。 具体目标2：GP-190的特性和功能分析：确定 GP-190在嗅觉神经元间前体和嗅觉间质传导中的作用 大脑皮层神经元。这些研究将确定一个长期的指导方针 分子对神经元的迁移，应该提供进一步的洞察力 神经元迁移的分子机制和有助于理解 大脑功能障碍的根本原因，如X-连锁Kallman综合征，精神障碍 发育迟缓和癫痫。

DESCRIPTION (Verbatim from the Applicant's Abstract): During development of the central nervous system, neurons born in proliferative zones migrate long distances to reach their final location. This process is essential for normal development and function of the nervous system. Disorders of neuronal migration play a causal role in abnormal development and dysfunction of the brain such as double cortex syndrome and epilepsy. Cerebral cortical neurons generated in the ventricular zone and subventricular zone (SVZ) migrate outward to the cortical plate along glia fibers. Olfactory interneuron precursors generated in the SVZ in the anterior forebrain (SVZa) migrate to the olfactory bulb in "chains," a process requiring the polysialic acid moiety of neural cell adhesion molecule (NCAM). The long-term goal is to elucidate the molecular mechanisms that regulate neuronal migration. The working hypothesis is that the migration of olfactory interneuron precursors and the cerebral cortical neurons is guided, in part, by an unidentified chemorepulsive factor. To test this hypothesis, the following specific aims are proposed. Specific Aim 1: Molecular cloning of the septum derived chemorepulsive factor by cloning the candidate molecule, gp-190. Specific Aim 2: Characterization and functional analysis of gp-190: Determine the role of gp-190 in the guidance of olfactory interneuron precursors and of cerebral cortical neurons. These studies would identify a long-range guidance molecule for migrating neurons and should provide further insight into molecular mechanisms of neuronal migration and contribute to the understanding of root causes of brain dysfunctions such as X-linked Kallman syndrome, mental retardation, and epilepsy.