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: 6476319
• 负责人: Lara Diane Hutson
• 金额: $ 4.42万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6476319
• 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其适当的目标。斑马鱼视网膜直肠神经元必须在复杂的环境中导航以找到其适当的目标。 斑马鱼视网膜直肠直肠项目是一个明确定义的系统，用于详细分析脊椎动物中的轴突路径。在下部脊椎动物中发育的视网膜轴突将视网膜在视神经头处退出，越过腹部中线，然后向后投射到对侧视觉底部，它们终止。在AshTray中，在最近的遗传筛选中产生的视网膜直截面突变体，一些视网膜轴突成功地导航到对侧视觉底部，但是许多视网膜轴突将许多视网膜轴突成功地导航到对侧光学上，但许多项目却导致了许多项目，以多种不适当的靶标。烟灰缸缺陷是眼自主的，表明突变的基因可能与视网膜轴突对探路线索的反应有关。该提案的四个目的旨在更好地了解烟灰缸影响视网膜轴突路径的机制。是否首先分析单个烟灰缸视网膜轴突的投影，以确定它们是否会使单个烟灰缸视网膜轴突的特定或分布式探路误差，以确定它们是否会造成特定或分布的探路误差或不适当的分支，还是造成烟灰板缺陷。其次，我将测试正确和错误注射的轴突是否来自视网膜神经节细胞的不同种群误入歧途。第三，我将测试正确和错误的轴突是否来自烟灰缸中视网膜神经节细胞的不同种群。第三，我将在体内分析生长锥行为和钙信号传导，以进一步了解误入性功能的机理。第四，我将在基因上误入歧途，测试候选基因误入歧途，并在必要时找到遗传功能。第四，我将在遗传上细烟灰缸，用于烟灰缸的测试候选基因，并在必要时找到在合理的烟灰缸内找到遗传标记，以启动染色体行走。从这些研究中获得的信息不仅应洞悉烟灰缸影响轴突指导的机制，还应介绍出正常视网膜轴突探路的机制。对正常探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。