Genetic control of dendritic tiling and morphogenesis

描述（由申请人提供）：该项目的目标是了解神经元如何建立其适当的树突场。为此，我们研究了黑腹果蝇（Drosophila melanogaster）周围神经系统（PNS）的树突平铺现象。在平纹系统中，如哺乳动物视网膜和果蝇PNS，功能相似的神经元的树突场表现出严格的回避，从而将一个大的接受区（分别是视网膜或体壁）划分为几个小区域。果蝇PNS中的多树突神经元由几个独立的平铺系统组成。我们正在测试这样一个假设，即这些系统中的每一个都提供并响应不同的排斥信号，这些排斥信号允许类树突识别和避开彼此，而不识别非类树突。我们已经开发了一系列细胞类型特异性标记物，可以用绿色荧光蛋白（GFP）独特地标记平铺神经元的不同子集。这些标记将用于：1)在活胚胎中观察神经元的消融研究，并检查邻近神经元树突区域的变化，2)检查候选基因在平铺中的作用，3)进行突变筛选，以识别和表征涉及平铺和树突形态发生的新基因。这些研究将确定树突乔木如何决定何时停止生长，何时继续或恢复生长，这些过程对于发育和再生过程中神经系统的正常连接至关重要。

DESCRIPTION (provided by applicant): The goal of this project is to understand how neurons establish their proper dendritic fields. For this purpose, we study the phenomenon of dendritic tiling in the peripheral nervous system (PNS) of Drosophila melanogaster. In tiled systems, such as the mammalian retina and Drosophila PNS, the dendritic fields of functionally similar neurons show strict avoidance, and thus partition a large receptive area (the retina or body wall, respectively) into several mini-domains. The multidendritic neurons in the Drosophila PNS comprise several independent tiled systems. We are testing the hypothesis that each of these systems provides and responds to distinct repulsive signals that allow like dendrites to recognize and avoid each other without recognizing non-like dendrites. We have developed a series of cell-type specific markers that uniquely label the distinct subsets of tiling neurons with Green Fluorescent Protein (GFP). These markers will be used to: 1) visualize neurons for ablation studies in live embryos and examine changes to the dendritic field areas of neighboring neurons, 2) examine candidate genes for their role in tiling and, 3) conduct a mutagenesis screen to identify and characterize novel genes involved in tiling and dendritic morphogenesis. These studies will identify how dendritic arbors decide when to stop growing and when to continue or resume their growth, processes that are essential for the proper wiring of nervous systems during development and regeneration.