ZEBRAFISH ASTRAY GENE AND RETINAL AXON PATHFINDING

脊椎动物大脑要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。斑马鱼的视顶板神经元必须在复杂的环境中导航，以找到合适的目标。斑马鱼视网膜项目是一个定义良好的系统，用于详细分析脊椎动物的轴突寻路。发育中的视网膜轴突在下部脊椎动物的视神经头部离开视网膜，穿过腹侧中线，然后向背侧投射到对侧视神经顶盖，并在那里终止。在烟灰缸中，视网膜顶叶寻路突变体在最近的基因筛选中产生，一些视网膜轴突成功导航到对侧视顶叶，但许多轴突投射到基因筛选中，一些视网膜轴突成功导航到对侧视顶叶，但许多轴突投射到大量不合适的目标。烟灰缸缺陷是眼睛自主的，这表明突变基因可能与视网膜轴突对寻路信号的反应有关。这一建议的四个目的是为了更好地理解烟灰缸影响视网膜轴突寻路的机制。它将首先分析单个烟灰缸视网膜轴突的投影，以确定它们是否产生特定的或分布的烟灰缸视网膜轴突的寻路错误，以确定它们是否产生特定的或分布的寻路错误，或者是否不适当的分支导致烟灰缸缺陷。其次，我将测试正确和不正确投射的轴突是否来自不同的视网膜神经节细胞群。第三，我将测试正确或不正确投射的轴突是否来自烟灰缸中不同的视网膜神经节细胞群。第三，我将分析生长锥行为和体内钙信号，以进一步了解误入功能的机制。第四，我将对误入歧途的基因进行精细定位，测试误入歧途的候选基因，如果有必要，找出基因功能。第四，我将对烟灰缸进行基因精细绘制，测试烟灰缸的候选基因，如果有必要，在烟灰缸的合理距离内找到基因标记，以启动染色体行走。从这些研究中获得的信息不仅可以深入了解烟灰缸影响轴突引导的机制，还可以深入了解正常视网膜轴突寻路的机制。对正常寻径行为的全面理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.