Characterizing Wnt Signaling Pathways in Axon Guidance

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形成的 在精确的解剖学和亚细胞位置上选择突触前和突触后神经元之间。虽然 在确定神经系统发育的关键轴突引导线索方面已经取得了巨大的进展 在过去的二十年里，轴突导向的信号传导和细胞生物学机制仍然部分地 明白对生长锥如何对特定线索做出反应的不完整知识阻碍了我们的能力 将轴突引导研究的知识应用于创伤性损伤后修复电路和恢复功能 以及神经退行性疾病。我们发现，Wnt家族形态原是轴突导向线索， 平面细胞极性通路介导Wnt在轴突导向中的功能。我们还发现Wnt信号调节 成年期脊髓损伤后轴突再生和平面细胞极性信号调节 神经元突触形成。我们计划使用Wnt/PCP信号作为解决未解决的基础问题的工具。 生长锥指导的问题，并了解其在成年轴突再生的扩大作用。目标1：如何实现 PCP组分产生不对称信号以介导生长锥在发育中的转向。目标二： Wnt/PCP通路与经典Wnt通路和Shh通路在A-P引导中的相互作用目的 3：Wnt/PCP信号在脊髓损伤后功能恢复中的作用。

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.