Characterizing Wnt Signaling Pathways in Axon Guidance

轴突引导中 Wnt 信号通路的特征

基本信息

批准号：
10815443
负责人：
YIMIN ZOU
金额：
$ 75.84万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-15 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10815443
关键词：
Actins Address Adult Affect Anatomy Animals Anterior Apical Axon Binding Proteins Biological CRISPR/Cas technology Caenorhabditis elegans Cells Chick Corticospinal Tracts Cues Dendrites Development Dorsal Drosophila genus Endocytosis FMR1 Family Floor Funding Genes Genetic Glutamates Growth Growth Cones Invertebrates Knock-in Mouse Knowledge LRRK2 gene Label Lead Length Lesion Location Manuscripts Maps Mediating Modeling Motor Neurodegenerative Disorders PARK8 gene Parkinson Disease Pathway interactions Phosphorylation Phosphotransferases Polymers Preparation Publications Recovery Recovery of Function Rodent Role SHH gene Sensory Signal Pathway Signal Transduction Spinal Cord Spinal Ganglia Spinal cord injury Synapses System Testing Time Traumatic injury Visual System WNT Signaling Pathway Work Yam - dietary Zebrafish axon growth axon guidance axon regeneration conditioning functional restoration glycosylation inhibitor injured morphogens nervous system development neural circuit planar cell polarity polymerization postsynaptic neurons presynaptic neurons recruit repaired response smoothened signaling pathway synaptogenesis tool

项目摘要

Neural circuits are formed by directed growth of axons and dendrites and subsequent assembly of synapses between selected pre- and postsynaptic neurons at precise anatomical and subcellular locations. Although tremendous progress has been made in identifying the key axon guidance cues for nervous system development in the past two decades, the signaling and cell biological mechanisms of axon guidance still remain partially understood. The incomplete knowledge of how growth cones signal to respond to specific cues hinders our ability to apply the knowledge from axon guidance studies to repair circuits and restore function after traumatic injury and in neurodegenerative disorders. We found that Wnt family morphogens are axon guidance cues and the planar cell polarity pathway mediates Wnt function in axon guidance. We also found that Wnt signaling regulate axon regrow after spinal cord injury in adulthood and planar cell polarity signaling regulates the assembly of glutamatergic synapse formation. We plan to use Wnt/PCP signaling as a tool to address unsolved fundamental questions in growth cone guidance and understand its expanded role in adult axon regeneration. Aim 1: How PCP components create asymmetric signaling to mediate growth cone turning in development. Aim 2: Interactions between Wnt/PCP pathway and canonical Wnt pathway and the Shh pathway in A-P guidance. Aim 3: Role of Wnt/PCP signaling in functional recovery after spinal cord injury.

神经回路是由轴突和树突的定向生长以及随后的突触组装而形成的在精确的解剖学和亚细胞位置，选定的前和突触后神经元之间。虽然在确定神经系统发展的关键轴突指导线索方面已取得了巨大进步在过去的二十年中，轴突引导的信号传导和细胞生物学机制仍然部分保持理解。关于生长锥如何响应特定提示的不完整知识阻碍了我们的能力应用轴突指导研究的知识来修复创伤后的电路和恢复功能以及神经退行性疾病。我们发现Wnt家族形态剂是轴突指导线索，而平面细胞极性途径介导了轴突指导中的Wnt功能。我们还发现Wnt信号调节成年后脊髓损伤后的轴突再生，平面细胞极性信号传导调节组装谷氨酸能突触的形成。我们计划使用Wnt/PCP信号作为解决未解决基本的工具生长锥指导中的问题，并了解其在成人轴突再生中的扩大作用。目标1：如何 PCP组件会产生不对称的信号传导，以介导开发中的生长锥。目标2： Wnt/PCP途径与规范Wnt途径与A-P指导中的SHH途径之间的相互作用。目的 3：WNT/PCP信号传导在脊髓损伤后功能恢复中的作用。