Axon Guidance in the Visual Systems of Drosophila

描述（由申请人提供）：大脑如何组织成 执行视觉信息处理的神经元回路 被质疑。在果蝇的大脑中，感光细胞轴突和 视神经节的皮质轴突形成精确的拓扑互连。 我们正在使用遗传学方法来识别参与 建立这种连接的架构。基因筛查的缺陷 视觉系统中神经元连接的建立导致了 在57个位点上恢复突变。包括在此集合中的是 突变影响的信号转导机制的分配 视觉原基中细胞的命运，以及轴突和 在连接建立期间的预期目标小区。我们将：1） 研究果蝇细胞粘连素家族成员在 控制神经元前体细胞对视网膜轴突传播的 分化信号，2）进行小规模筛选参与的基因座， 轴突连接的产生基于蛋白质定位， GFP基因陷阱转座子，3）进行突变的筛选，所述突变破坏了GFP基因陷阱转座子的表达。 板层突触电路的局部精细结构，并表征一些 4）分离eph和ephrin基因座的突变，并检查 对神经系统发育的影响考虑到 脊椎动物神经系统的机制和 无脊椎动物，这些研究可能会产生重要的见解， 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.