Signaling pathways controlling axon pathfinding

控制轴突寻路的信号通路

• 批准号: 6873530
• 负责人: YIMIN ZOU
• 金额: $ 27.84万
• 依托单位: UNIVERSITY OF CHICAGO
• 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/6873530
• 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（由申请人提供）：神经系统由大量神经元制成，恰好由轴突连接。该复杂的轴突网络对所有行为函数都很重要，并且在各种引导分子的控制下都在胚胎发生过程中建立。异常发育可能导致神经元联系的错误，从而导致各种神经系统疾病。长期目标是了解控制轴突在建筑神经回路中的定向生长的生长锥信号传导机制。了解轴突探路的基础机制可能为成年中枢神经系统肌轴突再生提供关键的工具。 Axon指导中的合并主题是，经常发现多个信号通路在一个单个神经元中起作用，这提出了一个基本问题，即信号通路如何集成在同一生长锥中，即位于轴突尖端的相同生长锥中，负责传感指导提示和生长锥转向。分别发现了两种主要的化学物质途径，Semaphorin/Neuropilin途径和缝隙/机器人途径。初步研究表明，两种信号通路之间存在意外的串扰。拟议的研究的目的是探索这两种主要的化学物质途径之间的串扰机制以及生长锥信号收敛的生物学意义。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。