Signaling pathways controlling axon pathfinding

控制轴突寻路的信号通路

• 批准号: 7329099
• 负责人: YIMIN ZOU
• 金额: $ 12.07万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7329099
• 关键词: biological signal transduction; cell surface receptors; chick embryo; developmental neurobiology; embryo /fetus tissue /cell culture; genetically modified animals; growth cones; laboratory mouse; nerve /myelin protein; neuronal guidance; neuropilins; protein binding; protein protein interaction

DESCRIPTION (provided by applicant): The nervous system is made of a large number of neurons, precisely connected by axons. This complex axonal network is important to all behavioral functions and is established largely during embryogenesis under the control of a variety of guidance molecules. Abnormal development may lead to errors in neuronal connections, causing various neurological and mental disorders. The long-term objective is to understand the growth cone signaling mechanisms controlling directional growth of axons in building neural circuits. Understanding molecular mechanisms underlying axon pathfinding may provide crucial tools for axonal regeneration in the adult central nervous system following injury. A merging theme in axon guidance is that multiple signaling pathways are frequently found to function in one single neuron, raising a fundamental question of how the signaling pathways are integrated in the same growth cone, the cellular apparatus located at the tip of the axon responsible for sensing guidance cues and growth cone steering. Two major chemorepellent pathways, the Semaphorin/Neuropilin pathway and the Slit/Robo pathway, were discovered separately. Preliminary studies suggest an unexpected crosstalk between the two signaling pathways. The goal of the proposed research is to explore the mechanism of the crosstalk between these two major chemorepellent pathways and the biological significance of growth cone signaling convergence. The proposed study will shed light on the organization of axon guidance signaling pathways and further the understanding of molecular mechanisms of nervous system development .

描述（申请人提供）：神经系统由大量神经元组成，通过轴突精确连接。这种复杂的轴突网络对所有行为功能都很重要，并且主要是在胚胎发生过程中在各种引导分子的控制下建立的。发育异常可能导致神经元连接错误，引起各种神经和精神障碍。长期目标是了解在构建神经回路时控制轴突定向生长的生长锥信号传导机制。了解轴突寻路的分子机制可能为成人中枢神经系统损伤后轴突再生提供重要工具。轴突引导中的一个合并主题是，经常发现多个信号传导途径在一个神经元中发挥作用，这就提出了一个基本问题：信号传导途径如何整合到同一生长锥中，该细胞装置位于轴突尖端，负责传感引导线索和生长锥转向。分别发现了两种主要的化学排斥途径：Semaphorin/Neuropilin 途径和 Slit/Robo 途径。初步研究表明这两个信号通路之间存在意想不到的串扰。本研究的目的是探索这两种主要化学排斥途径之间的串扰机制以及生长锥信号汇聚的生物学意义。拟议的研究将阐明轴突引导信号通路的组织，并进一步了解神经系统发育的分子机制。