MOLECULAR GUIDANCE OF NEURONAL MIGRATION

神经元迁移的分子指导

• 批准号: 6197391
• 负责人: YI RAO
• 金额: $ 27.66万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6197391
• 关键词: Xenopus; calcium; cell migration; chimeric proteins; gene mutation; gene targeting; genetically modified animals; laboratory mouse; nerve /myelin protein; neuronal guidance; protein structure function

DESCRIPTION (Verbatim from the Applicant's Abstract): Although cell migration is an essential step in neural development, our understanding of mechanisms underlying neuronal migration is still limited. This application focuses on cellular and molecular mechanisms guiding the direction of migratory neurons in the mammalian brain. In preliminary studies, we have demonstrated that the Slit family of secreted proteins can act as repulsive cues for migrating neurons. Together with previous findings by us and others that Slit is a chemorepellent for projecting axons, these results suggest that some mechanisms may be shared between axon guidance and neuronal migration. The availability of a guidance molecule for neuronal migration provides a foundation for our future studies of neuronal migration. We will dissect the functional domains of Slit and its receptor Robo to reveal whether the same domains are involved in axon guidance and neuronal migration. We will examine the roles of endogenous Slit in neuronal migration and axon guidance by using inhibitors. We will investigate subcellular and molecular components mediating the response of neurons to Slit. To reveal the role of specific Slit genes in neuronal migration and possibly in other developmental processes, we will use gene targeting to create a loss of function mutation in mouse Slit3 gene and analyze its consequences. The proposed experiments with interdisciplinary approaches should contribute to further understanding of the molecular mechanisms of neuronal migration.

描述（来自申请人摘要的逐字描述）：尽管细胞迁移 是神经发育的重要一步，我们对机制的理解 潜在的神经元迁移仍然有限。本申请集中于 细胞和分子机制指导迁移神经元的方向， 哺乳动物的大脑 在初步的研究中，我们已经证明了Slit家族分泌的 蛋白质可以作为迁移神经元的排斥性线索。连同 我们和其他人先前的发现表明，Slit是一种化学排斥剂， 这些结果表明，轴突之间可能共享一些机制， 引导和神经元迁移。指导分子的可用性， 神经元迁移为我们今后研究神经元迁移提供了基础。 迁移 我们将剖析Slit及其受体Robo的功能域， 是否相同的结构域参与轴突导向和神经元迁移。 我们将研究内源性Slit在神经元迁移和轴突再生中的作用。 使用抑制剂的指导。我们将研究亚细胞和分子 介导神经元对Slit的反应的组分。为了揭示 特异性Slit基因在神经元迁移和其他发育过程中的作用 在这一过程中，我们将使用基因靶向技术来创建一个功能缺失突变， 小鼠Slit3基因，并分析其后果。建议的实验， 跨学科方法应有助于进一步了解 神经元迁移的分子机制。