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

Dscam Dock 和 Cdc42 效应器在 Prosophilia 神经元树突发生中的作用

• 批准号: 8702810
• 负责人: Bo Huang
• 金额: $ 23.65万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-15 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8702810
• 关键词: Adaptor Signaling Protein; Biochemical; Biological Assay; Brain; Cell Adhesion Molecules; Cells; Cellular Structures; Collection; Complex; Coupling; Cues; Cytoskeleton; Data; Data Reporting; Dendrites; Disease; Down Syndrome; Down Syndrome Cell Adhesion Molecule; Drosophila genus; Embryo; Family; Fragile X Syndrome; Genetic; Growth; Growth Cones; Guanosine Triphosphate Phosphohydrolases; Image; Imaging technology; Knock-out; Knowledge; Lead; Learning; Life; Link; Literature; Maps; Mediating; Membrane; Methods; Microscopy; Molecular; Morphogenesis; Morphology; Motor Neurons; Neuraxis; Neurons; Pathogenesis; Pathway interactions; Positioning Attribute; Proteins; RNA Interference; Regulation; Research; Resolution; Role; Sampling; Signal Pathway; Signal Transduction; Site; Specific qualifier value; System; Testing; Time; Translating; Work; adapter protein; axon growth; base; extracellular; insight; intercellular cell adhesion molecule; netrin receptor; neurodevelopment; neuron development; neuronal circuitry; protein distribution; protein expression; public health relevance; rho; screening

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).

描述（由申请人提供）：我们的大脑通过相互连接的神经元的复杂和动态网络发挥作用。了解这种神经回路是如何建立和调节的，不仅是神经元发育研究的中心问题，也是了解神经发育障碍发病机制的关键。在果蝇胚胎aCC运动神经元中，我们的初步研究结果暗示了唐氏综合征细胞粘附分子（Dscam 1），细胞骨架活性调节剂，包括Cdc 42效应器，以及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Cdc 42效应子的膜富集促进和定位aCC树突状细胞发生。我们计划使用遗传和超分辨率显微镜方法相结合来测试这一假设。我们的项目包括三个目标：目的1，以检查Cdc 42效应膜积累的作用，在控制新的树突的位置，目的2，以阐明在aCC中的Dscam的机制，以指导Cdc 42效应的定位，目的3，通过Dscam 1-Dscam 1相互作用，了解来自伙伴神经元的细胞外线索。实现这些目标将提供深入了解Dscam功能的详细分子机制，特别是细胞-细胞识别如何通过细胞骨架动力学转化为CNS中的神经元形态发生，这在中枢神经系统（CNS）中一直是非常不足的探索。