CELL-CELL SIGNALING IN VISUAL DEVELOPMENT

描述(申请人提供)：视觉功能正常 系统需要从眼睛到大脑的神经连接才能精确地 已定义的空间顺序。除了遵循正确的路径外，连接 必须在地形图中排列：维护邻居关系，以便 视觉世界的空间精确图像是在大脑中形成的。 地形图被认为是对互补坡度的反应而形成的 突触前和突触后区域的位置标记，一种基于 主要介绍了半个多世纪以来对视觉视网膜顶盖的研究 投影。 近年来，一种新的细胞-细胞信号分子家族--肾上腺素， 已经被确认了。伊弗林在地形上具有特定的指导作用 视网膜轴突，是轴突投射有序发育所必需的 从视网膜到大脑。虽然具体的机制，甚至是广义的 视觉地图规范的原则仍然没有得到很好的描述， 将伊弗林识别为特定于地形的标记允许一个新的水平 在这一领域的分子研究。 这项提议的主要目标是研究人类免疫缺陷的分子机制。 视觉神经连接的发展。主要的关注点是依弗林和 它们的受体在视网膜顶盖系统的轴突引导和标测中。目标 方法包括：(1)分析视网膜轴突对肾上腺素的反应，或 顶盖膜，特别是通过新的体外分析，(2)作用和调节 包括转基因在内的在活体视觉地图开发中作为标记物的肾上腺素的研究 以及用于定向重组连接的新的小分子方法， (3)将肾上腺素信号转换为视网膜轴突反应的机制；(4) 在地图绘制中具有指导性或允许作用的其他线索，特别是 蛋白质酪氨酸磷酸酶及其配体。 虽然视觉地图历来是研究最多的，但地形图 是贯穿整个神经系统的主要组织原则。这些研究 希望在这里有助于对地图开发的基本理解 在分子水平上。这也应有助于提供一个基础 了解导致疾病的异常现象。最终，研究发现， 表征和调制新的细胞-细胞信号分子，可能导致 用于维持、修复或再生视力的治疗剂 关系。

DESCRIPTION (provided by the applicant): Correct functioning of the visual system requires neural connections from eye to brain to develop with precisely defined spatial order. In addition to following correct pathways, connections must be arranged in topographic maps: maintaining neighbor relationships so that spatially accurate images of the visual world are formed in the brain. Topographic maps are believed to develop in response to complementary gradients of positional labels in presynaptic and postsynaptic fields, an idea based mainly on more than half a century of research on the visual retinotectal projection. In recent years, a new family of cell-cell signaling molecules, the ephrins, has been identified. Ephrins have topographically specific guidance effects on retinal axons, and are required for orderly development of axon projections from the retina to the brain. While specific mechanisms, and even broad principles, of visual map specification remain poorly characterized, the identification of ephrins as topographically specific labels allows a new level of molecular investigation in this field. The broad goal of this proposal is to investigate molecular mechanisms in development of visual neural connections. The major focus is on ephrins and their receptors in axon guidance and mapping in the retinotectal system. Aims and methods include: (1) Analysis of retinal axon responses to ephrins, or tectal membranes, especially by new in vitro assays, (2) Action and modulation of ephrins as labels in visual map development in vivo, including transgenic and new small-molecule approaches for directed restructuring of connections, (3) Mechanisms that convert ephrin signaling to retinal axon responses, (4) Other cues with instructive or permissive roles in mapping, particularly protein tyrosine phosphatases and their ligands. While visual maps have historically been the best studied, topographic mapping is a major organizational principle throughout the nervous system. The studies here are expected to contribute to the basic understanding of map development at the molecular level. This should also help in providing a basis to understand abnormalities that lead to disease. Ultimately, studies to identify, characterize, and modulate novel cell-cell signaling molecules, may lead to therapeutic agents for maintenance, repair or regeneration of visual connections.