NEURONAL PATTERNS IN THE DEVELOPING VISUAL SYSTEM

视觉系统发育中的神经元模式

• 批准号: 3260409
• 负责人: STEVEN C MCLOON
• 金额: $ 7.42万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1992-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3260409
• 关键词: axon; biological information processing; biomarker; chick embryo; fluorescence; genetic library; growth cones; immunochemistry; molecular cloning; monoclonal antibody; neurogenesis; neuronal guidance; nucleic acid hybridization; optic chiasmas; optic tract; peptide chemical synthesis; protein purification; retina; retinal ganglion; surface antigens; tissue /cell culture; transfection; visual pathways; visual stimulus

DESCRIPTION (Investigator's Abstract): The axons of retinal ganglion cells project to the central visual nuclei in the brain in a topographic pattern, such that the two dimensional pattern of the ganglion cells in the retina is approximately recreated in the pattern of their terminals in the visual nuclei. Alteration of this pattern results in the ineffective processing of visual information and an inability to respond to visual stimuli in a meaningful manner. The mechanism responsible for development of the topographic pattern of connections is unknown. One hypothesis suggests that axons carry specific molecules that act as positional labels. The interaction between positionally labeled retinal axons and tectal cells with complimentary labels could determine the pattern in which connections develop. The goal of this project is to identify differences between axons growing from the nasal and temporal sides of the developing chick retina that might reflect positional labels. The initial steps of the project will concentrate on characterization of anatomical and molecular differences between the two groups of axons. The long term goal is to understand functional differences that account for development of the specific pattern of axon growth and synapse formation exhibited by retinal axons. The project is divided into four specific aims. First, TRAP, a molecule expressed on most temporal but few nasal retinal axons, will be characterized in more detail. This will involve cloning the gene for TRAP from a cDNA library, sequencing the gene, and developing antibodies to the protein for use in analyzing the function of TRAP. Second, three complementary approaches will be used to identify other molecules expressed asymmetrically between the nasal and temporal sides of the developing retina. These approaches include the use of monoclonal antibodies, subtractive cDNA hybridization, and lectin blots. As molecules are discovered, they will be characterized as described for TRAP. Third, anatomical differences in the pattern of growth between nasal and temporal retinal axons will be identified. This information will be used to develop in vivo assays to study the function of side specific molecules, and may also supply insights into functional differences between nasal and temporal axons. Fourth, the function of molecules asymmetrically expressed in the developing retina will be examined. This will involve perturbing the function of these molecules with antibodies in vivo and in vitro. Preliminary studies will also evaluate techniques for introducing genes to alter the expression of specific molecules. This project will have a significant impact on the investigators future ability to reconnect retinal axons with the brain in a useful manner in order to cure blindness.

描述（研究者摘要）：视网膜神经节细胞的轴突 投射到大脑中的中央视觉核团， 使得视网膜中神经节细胞的二维图案 在视觉上， 原子核。 这种模式的改变导致无效处理 视觉信息和无法对视觉刺激作出反应， 有意义的方式。 负责发展的机制 连接的地形模式未知。 一种假设认为 轴突携带特定的分子作为位置标记。 的 位置标记的视网膜轴突与顶盖细胞的相互作用 可以决定连接的模式， 开发. 这个项目的目标是确定轴突之间的差异 从发育中的小鸡视网膜的鼻侧和颞侧生长 可能反映位置标签的信息。 项目的初始步骤 将专注于解剖学和分子生物学的特征 两组轴突之间的差异。 长期目标是 了解功能差异，说明发展的 视网膜神经元轴突生长和突触形成的特殊模式 轴突 该项目分为四个具体目标。 第一，陷阱，a 在大多数颞侧但少数鼻侧视网膜轴突上表达的分子， 更详细地描述。 这将涉及克隆TRAP基因 从cDNA文库中，对基因进行测序，并开发针对 用于分析TRAP功能的蛋白。 二、三 互补的方法将用于鉴定表达的其他分子， 鼻侧和颞侧之间不对称的发展 视网膜。 这些方法包括使用单克隆抗体， 消减cDNA杂交和凝集素印迹。 就像分子 发现后，它们将如TRAP所述进行表征。 第三、 鼻和颞骨生长模式的解剖学差异 将识别视网膜轴突。 这些信息将用于开发 研究侧特异性分子的功能的体内测定，并且可以 还提供了对鼻和颞之间的功能差异的见解 轴突 第四，分子的功能不对称地表达在 将检查发育中的视网膜。 这将涉及扰乱 这些分子与抗体在体内和体外的功能。 初步研究还将评估将基因引入 改变特定分子的表达。 该项目将有一个 对研究者未来重新连接视网膜的能力产生重大影响 神经轴突与大脑的一个有用的方式，以治疗失明。