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 为了研究轴突生长背后的细胞和分子事件， 寻路和目标细胞识别。发育中的视网膜产生 三种主要类型的光感受器神经元具有明确的模式 差异化。它们的轴突生长锥体穿过很长的距离 在通往具体目标的过程中做出一些刻板印象的寻路决定 目标是大脑发育中的视神经节内的目标。 在这些神经节细胞层内，光感受器轴突与靶细胞相连。 神经元以精确的视网膜定位顺序排列。我们计划用强大的 在果蝇中可用的遗传、细胞和分子方法 了解这种视网膜原位连接模式是如何建立的。 我们的初步研究表明，位置引导线索在 视网膜轴突引导。这些研究揭示了视网膜病变的特点。 果蝇视觉系统中的图案形成让人想起 在低等脊椎动物中长期研究的视网膜顶盖系统。此外，我们 分离了视网膜轴突所需的10个基因的突变 指导。在这里，我们提议进行实验，旨在进一步表征 这些基因的细胞和发育功能及其生化 其产品的功能。将使用马赛克分析来识别 需要这些基因功能的细胞。选定的遗传基因座 将在分子水平上进行分离和表征。我们还提议 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，我们想出了一种方法 它利用毒素基因的有条件表达来消融特定的 发育过程中的细胞。这种方法将被用来检验 为发育中的大脑中的各种细胞群提供指导 视网膜轴突的线索。这些对果蝇的研究很可能会 对神经元的精确模式如何产生重要见解 眼睛和大脑之间的连接建立在视觉系统中 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.