AXON GUIDANCE IN THE VISUAL SYSTEM OF DROSOPHILA

果蝇的视觉系统提供了一个独特的机会 为了检查轴突生长背后的细胞和分子事件， 寻路和靶细胞识别。发育中的视网膜产生 三种主要类型的感光神经元在一个明确的模式， 分化它们的轴突生长锥跨越很长的距离， 在前往特定目的地的途中， 大脑发育中的视神经节内的目标目的地。 在这些神经节细胞层内，感光器轴突连接到靶细胞， 神经元按照视网膜位置的顺序排列。我们计划利用强大的 遗传学、细胞学和分子学方法， 理解这种视网膜定位连接模式是如何建立的。 我们的初步研究表明， 视网膜轴突引导这些研究揭示了视网膜病变的特征， 果蝇视觉系统中的模式形成， 长期以来在低等脊椎动物中研究的视网膜顶盖系统。另外我们 在视网膜轴突所需的10个基因中发现了突变 指导在这里，我们提出了旨在进一步表征 这些基因的细胞和发育功能以及生物化学 其产品的功能。马赛克分析将用于识别 这些基因的功能是必需的。选择的遗传位点 将在分子水平上被分离和表征。我们亦建议 分离视网膜轴突导向突变体的第二种方法， 将允许恢复导致致命缺陷的突变， 胚胎神经系统发育最后，我们设计了一种方法， 它利用毒素基因的条件表达来消除特定的 细胞发育过程中。此方法将用于检查 发育中的大脑中的各种细胞群 视网膜轴突的线索这些在果蝇身上的研究很可能 对神经元的精确模式 眼睛和大脑之间的联系是在视觉系统中建立的 包括人类在内的脊椎动物。

The visual system of the fruitfly, Drosophila, offers a unique opportunity to examine the cellular and molecular events underlying axon outgrowth, pathfinding and target cell recognition. The developing retina produces three major types of photoreceptor neurons in a well-defined pattern of differentiation. Their axonal growth cones traverse long distances and make a number of stereotypic pathfinding decisions en route to specific target destinations within the developing optic ganglia of the brain. Within these ganglion cell layers, photoreceptor axons connect to target neurons in a precise retinotopic order. We plan to use the powerful genetic, cellular, and molecular methods available in Drosophila to understand how this retinotopic connection pattern is established. Our preliminary studies have implicated positional guidance cues in retinal axon guidance. These studies reveal features of retinotopic pattern formation in the Drosophila visual system that are reminiscent of the retinotectal system long studied in lower vertebrates. In addition, we have isolated mutations in ten genes that are required for retinal axon guidance. Here we propose experiments aimed at further characterizing the cellular and developmental functions of these genes and the biochemical functions of their products. Mosaic analysis will be used to identify the cells in which these gene functions are required. Selected genetic loci will be isolated and characterized at the molecular level. We also propose a second approach to the isolation of retinal axon guidance mutants that will permit the recovery of mutations which result in lethal defects in embryonic nervous system development. Finally, we have devised a method that employs the conditional expression of a toxin gene to ablate specific cells during development. This method will be used to examine the roles of various cell populations in the developing brain in providing guidance cues to retinal axons. It is likely that these studies in Drosophila will yield important insights into how the precise pattern of neuronal connections between the eye and brain is established in the visual systems of vertebrates, including humans.