ROLE OF EXTRACELLULAR MATRIX IN NEURAL DEVELOPMENT

细胞外基质在神经发育中的作用

• 批准号: 3416671
• 负责人: Dale Hunter
• 金额: $ 16.68万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3416671
• 关键词: antibody; cell adhesion; cell differentiation; cell type; cerebral cortex; developmental neurobiology; extracellular matrix; extracellular matrix proteins; fibronectins; gene expression; genetic regulation; genetically modified animals; guinea pigs; in situ hybridization; laboratory mouse; laboratory rat; laminin; messenger RNA; molecular biology; molecular cloning; neurons; olfactory lobe; polymerase chain reaction; protein purification; receptor; synaptogenesis; tissue /cell culture; transfection

Environmental cues play a major role in determining the ultimate fate of the developing nervous system. Our goals are to identify some of the signals recognized by developing neurons as they migrate, differentiate, and form synaptic connections. Previously, as a postdoctoral fellow in the laboratory of Joshua Sanes at Washington University, I identified a component of the synaptic basal lamina of the neuromuscular junction, s-laminin, that is likely to be involved in the stabilization of the mature motor synapse. I obtained antibodies to and cDNA clones for this extracellular matrix molecule, and we are currently developing similar resources for other potentially neuroactive molecules. We plan on using both previously and newly generated antibodies as immunohistochemical and immunopurification tools for identifying the location and function of matrix molecules in the developing nervous system. Similarly, we plan on using previously and newly generated cDNA probes to examine the expression and regulation of these molecules during development. We propose to use immunohistochemical and molecular biological methods to determine where and when s-laminin is expressed in the developing cerebral cortex and olfactory system, and to determine the function of s-laminin in these areas during development, using both in vitro and in vivo systems. In addition, we propose to identify the neural receptor for s-laminin, using purified s-laminin and s-laminin-derived peptides as affinity reagents. Finally, we propose to identify and characterize other matrix components that may be important determinants of development in the central nervous system, using both immunohistochemical and molecular biological techniques. Together, these lines of investigation should help to define the role of extracellular matrix molecules in the development and differentiation of the nervous system.

环境线索在确定最终命运方面起着重要作用 发育中的神经系统。 我们的目标是确定一些 当神经元迁移，区分，通过发展神经元认可的信号 并形成突触连接。 以前，作为博士后家伙 华盛顿大学约书亚·萨内斯（Joshua Sanes）实验室，我确定了 神经肌肉连接的突触基底层的成分， S-氯宁蛋白，可能与稳定有关 成熟的运动突触。 我获得了对此的抗体和cDNA克隆 细胞外基质分子，我们目前正在发展相似 其他潜在神经活性分子的资源。 我们计划使用 以前和新生成的抗体作为免疫组织化学 以及用于识别位置和功能的免疫治疗工具 发育中神经系统中基质分子的。 同样，我们 计划使用以前的和新生成的cDNA探针检查 这些分子在发育过程中的表达和调节。 我们建议使用免疫组织化学和分子生物学方法 确定在发育中表达s层蛋白的何时何地 大脑皮层和嗅觉系统，并确定 在开发过程中，在这些区域中使用体外和中 体内系统。 另外，我们建议识别神经受体 对于S-氯宁蛋白，使用纯化的S-层蛋白和S层蛋白衍生的肽 作为亲和力试剂。最后，我们建议识别和表征 其他可能是重要决定因素的矩阵组件 中枢神经系统的发展，同时使用 免疫组织化学和分子生物学技术。 一起， 这些调查方案应有助于定义 细胞外基质分子在开发和分化中 神经系统。