The Role of Dscam Dock and Cdc42 Effectors in Prosophilia Neuron Dendritogenesis

描述（由申请人提供）：我们的大脑通过相互连接的神经元组成的复杂动态网络发挥作用。了解这种神经回路是如何建立和调控的，不仅是神经元发育研究的核心问题，也是理解神经发育障碍发病机制的关键。在果蝇胚胎的aCC运动神经元中，我们的初步发现提示了唐氏综合征细胞粘附分子（Dscam1）、细胞骨架活性调节因子（包括Cdc42效应物）与树突生长的定位和启动之间的联系。因此，我们假设Dscam细胞间相互作用通过Cdc42效应物的膜富集促进和定位aCC树突发生。我们计划使用遗传和超分辨率显微镜相结合的方法来验证这一假设。我们的项目包括三个目标：目的1研究Cdc42效应膜积累在控制新树突位置中的作用，目的2阐明aCC中Dscam引导Cdc42效应物定位的机制，目的3通过Dscam1-Dscam1相互作用了解来自伴侣神经元的细胞外信号。实现这些目标将提供对Dscam功能的详细分子机制的见解，特别是如何通过细胞骨架动力学将细胞-细胞识别转化为中枢神经系统中的神经元形态发生，这在中枢神经系统（CNS）中尚未得到充分探索。

DESCRIPTION (provided by applicant): Our brains function through complex and dynamic networks of interconnected neurons. Understanding how this neuronal circuitry is established and regulated is not only the central question of neuron development studies, but also the key to understand the pathogenesis of neurodevelopment disorders. In the aCC motoneuron of Drosophila embryo, our preliminary findings have hinted the connection among the Down syndrome cell adhesion molecule (Dscam1), cytoskeleton activity regulators including Cdc42 effectors, and the positioning and initiating of dendrite growth. Therefore, we hypothesize that Dscam intercellular interaction promotes and positions aCC dendritogenesis through membrane enrichment of Cdc42 effectors. We plan to test this hypothesis using a combination of genetic and super-resolution microscopy methods. Our project consists of three aims: Aim 1 to examine the role of Cdc42 effector membrane accumulation in controlling the position of new dendrites, Aim 2 to elucidate the mechanism for Dscam in aCC to guide the positioning of Cdc42 effectors, and Aim 3 to understand the extracellular cue from partner neurons through Dscam1-Dscam1 interaction. Accomplishing these aims will provide insights into the detailed molecular mechanisms of Dscam function, especially how cell-cell recognition is translated through cytoskeleton dynamics into neuron morphogenesis in CNS, which has been very much under-explored in the central nervous system (CNS).