ZEBRAFISH ASTRAY GENE AND RETINAL AXON PATHFINDING

描述脊椎动物的大脑为了获得功能所需的特定连接，数百万神经元的轴突必须在复杂的环境中导航，以找到合适的目标。斑马鱼的视网膜顶盖神经元必须在复杂的环境中导航，才能找到合适的目标。斑马鱼视网膜顶盖项目是一个定义明确的系统，用于详细分析脊椎动物的轴突路径。低等脊椎动物发育中的视网膜轴突在视神经头部离开视网膜，穿过腹中线，然后向背侧投射到对侧视顶盖，在那里它们终止。在烟灰缸中，一些视网膜轴突成功地导航到对侧视顶盖，但许多投射到遗传屏幕，一些视网膜轴突成功地导航到对侧视顶盖，但许多投射到许多不合适的靶点。烟灰缸缺陷是眼睛自主的，这表明突变的基因可能参与了视网膜轴突对寻路线索的反应。这项建议的四个目的是为了更好地了解烟灰缸影响视网膜轴突路径的机制。IF将首先分析单个烟灰缸视网膜轴突的投射，以确定它们是对单个烟灰缸视网膜轴突进行特定的还是分布式的寻径错误，以确定它们是做出特定的还是分布式的寻径错误，或者是否不适当的分支导致烟灰缸缺陷。其次，我将测试正确和错误地投射轴突是否来自迷失方向的不同群体的视网膜神经节细胞。第三，我将测试正确和错误地投射轴突是否来自烟灰缸中不同数量的视网膜神经节细胞。第三，对生长激素在体内的行为和钙信号进行分析，以进一步了解迷失功能的机制。第四，我将在基因上精细定位迷失方向，测试候选基因是否迷失方向，如果有必要，还会找到遗传功能。第四，我将对烟灰缸进行基因精细定位，测试候选基因的烟灰缸，如果有必要的话，在离烟灰缸合理距离内找到遗传标记，用来开始染色体行走。从这些研究中获得的信息不仅应该为烟灰缸影响轴突引导的机制提供洞察，也应该为正常视网膜轴突路径寻找的机制提供洞察力。对正常寻路行为的全面了解将有助于理解神经再生的机制，并可能阐明人类发育障碍的基础。

DESCRIPTION For the vertebrate brain to acquire the specific connections necessary for function, the axons of millions of neurons must navigate through complex environments to find their appropriate targets. The zebrafish retinotectal neurons must navigate through complex environments to find their appropriate targets. The zebrafish retinotectal project is a well-defined system for detailed analysis of axon pathfinding in a vertebrate. Developing retinal axons in lower vertebrates exit the retina at the optic nerve head, cross the ventral midline, and then project dorsally to the contralateral optic tectum where they terminate. In ashtray, a retinotectal pathfinding mutant generated in a recent genetic screen, some retinal axons navigate successfully to the contralateral optic tectum, but many project to a genetic screen, some retinal axons navigate successfully to the contralateral optic tectum, but many project to a multitude of inappropriate targets. The ashtray defect is eye-autonomous, suggesting that the mutated gene may be involved in retinal axon responses to pathfinding cues. The four aims of this proposal are designed to gain a better understanding of the mechanism by which ashtray affects retinal axon pathfinding. If will first analyze the projections of individual ashtray retinal axons in order to determine whether they make specific or distributed pathfinding errors of individual ashtray retinal axons in order to determine whether they make specific or distributed pathfinding errors or whether inappropriate branching is responsible for the ashtray defect. Second, I will test whether correctly- and incorrectly-projecting axons arise from distinct populations of retinal ganglion cells in astray. Third, I will test whether correctly- and incorrectly-projecting axons arise from distinct populations of retinal ganglion cells in ashtray. Third, I will analyze growth cone behavior and calcium signaling in vivo in order to gain further insight into the mechanism of astray function. And fourth, I will genetically fine-map astray, test candidate genes for astray, and if necessary, find genetic function. And fourth, I will genetically fine-map ashtray, test candidate genes for ashtray, and if necessary, find genetic markers within a reasonable distance of ashtray with which to initiate a chromosome walk. The information gained from these studies should provide insight not only into the mechanism by which ashtray affects axon guidance, but also into the mechanisms of normal retinal axon pathfinding. A comprehensive understanding of normal pathfinding behavior will contribute to understanding the mechanisms by which nerves regenerate, and may illuminate the basis for human developmental disorders.