CELL-CELL SIGNALING IN VISUAL DEVELOPMENT

描述（由申请人提供）：目视检查的正确功能 系统需要从眼睛到大脑的神经连接， 空间秩序。除了遵循正确的路径，连接 必须安排在地形图：保持邻居关系， 视觉世界的空间精确图像在大脑中形成。 地形图的发展被认为是对互补梯度的响应 位置标签在突触前和突触后领域，一个想法， 主要介绍了半个多世纪来对视觉视网膜顶盖的研究 投影 近年来，一个新的细胞-细胞信号分子家族，肝配蛋白， 已经被确认了肝配蛋白具有地形特异性的指导作用， 视网膜轴突，并需要有序发展的轴突投影 从视网膜到大脑虽然具体的机制，甚至广泛的 原则，视觉地图规范仍然很差的特点， 将肝配蛋白鉴定为地形特异性标记物 最重要的分子研究 这项提议的主要目标是研究 视觉神经连接的发展。主要的焦点是ephrins和 它们的受体在视网膜顶盖系统的轴突导向和映射中的作用。旨在 和方法包括：（1）分析视网膜轴突对肝配蛋白的反应，或 顶盖膜，特别是通过新的体外测定，（2）作用和调节 在体内视觉图谱开发中作为标记的肝配蛋白， 和新的小分子方法来定向重组连接， (3)将ephrin信号转换为视网膜轴突反应的机制，（4） 其他具有指导性或许可性作用的线索，特别是 蛋白酪氨酸磷酸酶及其配体。 虽然视觉地图在历史上一直是最好的研究， 是整个神经系统的主要组织原则。研究 希望有助于对地图开发的基本理解 在分子水平上。这也将有助于提供一个基础， 了解导致疾病的异常。最终，研究确定， 表征和调节新的细胞-细胞信号分子，可能导致 用于维持、修复或再生视觉障碍的治疗剂 连接.

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.