Axon Guidance in the Visual Systems of Drosophila

描述(申请人提供)：大脑是如何组织成 执行视觉信息处理的神经元电路有很长一段时间 一直备受质疑。在果蝇的大脑中，光感受器细胞轴突和 视神经节的皮质轴突形成精确的地形图互连。 我们正在使用一种遗传方法来识别参与 这种连接架构的建立。基因筛查中的缺陷 视觉系统中神经元连接的建立导致了 57个基因座的突变恢复。包括在此集合中的 影响信号转导机制的突变 视觉原基中的细胞命运，以及轴突和 在建立连通性期间预期的目标小区。我们将：1) 果蝇细胞粘附素家族成员的功能研究 控制神经前体细胞对视网膜轴突的反应 分化信号，2)对涉及的基因座进行小范围筛选 基于蛋白质定位的轴突连通性的产生 GFP基因陷阱转座子，3)进行突变筛选，破坏 板层突触回路的局部精细结构，并描述了一些 确定基因座，4)分离Eph和EPhin基因座的突变，并检查 它们对神经系统发育的影响。考虑到守恒性 在形成脊椎动物神经系统模式的机制和 对于无脊椎动物，这些研究可能会对 脊椎动物大脑复杂结构的发展， 包括人类。

DESCRIPTION (provided by applicant): How the brain is organized into the neuronal circuits that carry out the processing of visual information has long been in question. In the brain of Drosophila, photoreceptor cell axons and the cortical axons of the optic ganglia form precise topographic interconnections. We are using a genetic approach to identifying the molecules involved in the establishment of this connective architecture. A genetic screen for defects in the establishment of neuronal connectivity in the visual system resulted in the recovery of mutations at fifty-seven loci. Included in this collection are mutations that affect the signaling mechanisms underlying the assignment of cell fate in the visual primordia, and interactions between axons and prospective target cells during the establishment of connectivity. We will: 1) study the function of a Drosophila member of the Cytohesin family in controlling the response of neuronal precursor cells to retinal axon-borne differentiation signals, 2) conduct a small-scale screen for loci involved in the generation of axonal connectivity based on protein localization reported by a GFP gene-trap transposon, 3) perform a screen for mutations that disrupt the local fine structure of lamina synaptic circuitry and characterize some of the loci identified, 4) isolate mutations at the eph and ephrin loci, and examine their consequences for nervous system development. Given the conservation between the mechanisms that pattern the nervous systems of vertebrates and invertebrates, these studies will likely yield important insights into the development of the complex architectures of the brains of vertebrates, including humans.