Genetic control of dendritic tiling and morphogenesis

描述(申请人提供)：本项目的目标是了解神经元如何建立其适当的树突区。为此，我们研究了果蝇外周神经系统(PNS)中的树突状瓦片现象。在瓦片系统中，如哺乳动物的视网膜和果蝇的PNS，功能相似的神经元的树突区域表现出严格的回避，从而将一个大的感受区(分别是视网膜或体壁)划分为几个微域。果蝇三叉神经节内的多树突神经元由几个独立的瓦状系统组成。我们正在测试一种假设，即这些系统中的每一个都提供并响应不同的排斥信号，这些信号允许相似的树突识别和避免彼此，而不识别不同的树突。我们已经开发了一系列细胞类型的特异性标记，用绿色荧光蛋白(GFP)唯一地标记了不同的瓦状神经元亚群。这些标记将用于：1)显示活体胚胎中用于消融研究的神经元，并检查相邻神经元树突野区域的变化；2)检查候选基因在瓦片中的作用；以及3)进行突变筛选，以识别和表征与瓦片和树突形态发生有关的新基因。这些研究将确定树枝如何决定何时停止生长以及何时继续或恢复生长，这些过程对于发育和再生期间神经系统的正确连接至关重要。

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.