ZEBRAFISH ASTRAY GENE AND RETINAL AXON PATHFINDING

斑马鱼迷路基因和视网膜轴突寻路

• 批准号: 6055154
• 负责人: Lara Diane Hutson
• 金额: $ 3.03万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6055154
• 关键词: axon; biological signal transduction; calcium flux; cell population study; developmental genetics; developmental neurobiology; gene mutation; genetic mapping; growth cones; neurogenetics; neuronal guidance; retinal ganglion; zebrafish

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.

描述 为了使脊椎动物大脑获得功能所需的特定连接，数百万个神经元的轴突必须在复杂的环境中导航以找到适当的目标。斑马鱼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寻路。低等脊椎动物正在发育的视网膜轴突在视神经乳头处离开视网膜，穿过腹侧中线，然后向后投射到对侧视顶盖，并在那里终止。在烟灰缸中，在最近的基因筛选中产生的视网膜顶盖寻路突变体，一些视网膜轴突成功导航到对侧视顶盖，但许多投射到基因筛选，一些视网膜轴突成功导航到对侧视顶盖，但许多投射到多个不适当的目标。烟灰缸缺陷是眼睛自主的，表明突变基因可能参与视网膜轴突对寻路线索的反应。该提案的四个目标旨在更好地理解烟灰缸影响视网膜轴突寻路的机制。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或分布式寻路错误。 。其次，我将测试正确和错误投射的轴突是否来自误入歧途的不同视网膜神经节细胞群。第三，我将测试正确和错误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，我将分析体内生长锥行为和钙信号传导，以进一步了解迷失功能的机制。第四，我将对迷失的基因进行精细定位，测试迷失的候选基因，并在必要时寻找遗传功能。第四，我将对烟灰缸进行基因精细图谱，测试烟灰缸的候选基因，并在必要时在烟灰缸合理距离内找到遗传标记，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，而且还可以深入了解正常视网膜轴突寻路的机制。对正常寻路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。