CELL-CELL SIGNALING IN VISUAL DEVELOPMENT

视觉发育中的细胞信号传导

• 批准号: 6800781
• 负责人: John G Flanagan
• 金额: $ 43.88万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2006-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6800781
• 关键词: axon; brain mapping; cell cell interaction; cell free system; chick embryo; ephrins; immunofluorescence technique; in situ hybridization; intercellular connection; laboratory mouse; molecular cloning; neuroanatomy; neuronal guidance; northern blottings; polymerase chain reaction; protein structure function; protein tyrosine phosphatase; receptor binding; receptor sensitivity; retina; synaptogenesis; axon; brain mapping; cell cell interaction; cell free system; chick embryo; ephrins; immunofluorescence technique; in situ hybridization; intercellular connection; laboratory mouse; molecular cloning; neuroanatomy; neuronal guidance; northern blottings; polymerase chain reaction; protein structure function; protein tyrosine phosphatase; receptor binding; receptor sensitivity; retina; synaptogenesis

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.

描述（申请人提供）：视觉的正确功能 系统需要从眼到大脑的神经联系才能精确发展 定义的空间顺序。除了遵循正确的途径，连接 必须在地形图中安排：维护邻居关系 视觉世界的空间准确图像是在大脑中形成的。 据信地形图会响应互补梯度而发展 突触前和突触后场中的位置标签，这是一个基于想法的 主要是在半个多世纪的视觉视网膜上进行的研究 投影。 近年来，一个新的细胞 - 细胞信号分子家族，ephrins， 已经确定了。以弗所具有对地形的指导影响 视网膜轴突，是有序开发轴突投影所必需的 从视网膜到大脑。而特定的机制，甚至广泛 视觉地图规范的原理的特征仍然很差， 鉴定以弗林作为地形特定标签允许新级别 该领域的分子研究。 该提案的广泛目标是研究分子机制 开发视觉神经联系。主要重点是以弗林和 它们的受体在视网膜直肠系统中的轴突引导和映射中。目标 和方法包括：（1）视网膜轴突对ephrins的反应，或 剖面膜，特别是通过新的体外测定法，（2）作用和调节 在体内的视觉图开发中，以ephrins为标签，包括转基因 以及用于定向连接重组的新小分子方法 （3）将ephrin信号传导转化为视网膜轴突反应的机制，（4） 其他提示在映射中具有启发性或宽松的作用，尤其是 蛋白酪氨酸磷酸酶及其配体。 尽管视觉地图历史上是研究最好的，但地形映射 是整个神经系统的主要组织原则。研究 期望这有助于对地图开发的基本理解 在分子水平。这也应该有助于提供基础 了解导致疾病的异常。最终，确定的研究， 表征和调节新型细胞 - 细胞信号分子，可能导致 视觉维护，维修或再生的治疗剂 连接。