FUNCTIONAL ORGANIZATION OF THE VISUAL SYSTEM

视觉系统的功能组织

• 批准号: 2157961
• 负责人: ALAN L. PEARLMAN
• 金额: $ 14.08万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-08-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2157961
• 关键词: cell migration; cellular polarity; chondroitin sulfates; developmental neurobiology; embryo /fetus tissue /cell culture; extracellular matrix; fibronectins; glia; immunologic assay /test; in situ hybridization; integrins; laboratory mouse; neuroanatomy; neuronal guidance; protease inhibitor; proteoglycan; visual cortex

Neuronal migration is a critical step in forming the laminar structure of the visual cortex, but the molecular signals that guide migration and determine final neuronal position are unknown. To determine the role of extracellular matrix (ECM) components in these processes, we have analyzed their spatiotemporal distribution in the cortex of the mouse. Our recent findings are: i) The ECM glycoprotein fibronectin (FN) is distributed along the processes of radial glia where they pass through the preplate/subplate neurons; both FN and chondroitin sulfate proteoglycans (CSPGs) are closely associated with these neurons. These observations suggest that ECM of radial glia is involved in glial-guided migration, and that the ECM surrounding preplate/subplate neurons is a framework for cortical plate formation. ii) Arriving thalamic afferent axons follow a path through the subplate that contains abundant CSPGs, suggesting that CSPGs help to determine the molecular specificity of the pathway. iii) FN is produced in two distinct phases of cortical development, first by cells of the neuroepithelium which include radial glia, and then by a subset of migrating neurons as they approach and enter the cortical plate. To test hypotheses regarding the functional role of ECM components in neuronal migration, we have developed an organotypic slice preparation that preserves embryonic layers, radial glia, and ECM components for several days in a serum-free medium. Neurons divide in the ventricular zone and migrate into the cortical plate in this preparation, and antibodies penetrate the slice. As the next stage of the analysis we will further characterize specific extracellular matrix components present in the developing visual cortex and determine which cells produce individual components. We will use the organotypic slice preparation to determine which cell-surface and extracellular matrix components play a role in neuronal migration by perturbing their function experimentally. Definition of the cellular and -molecular mechanisms underlying neuronal migration will provide a foundation for understanding the abnormalities of cortical lamination that are common manifestations of insults to the brain in early human development.

神经元迁移是形成层状结构的关键步骤 视觉皮层，但引导迁移的分子信号 并确定最终的神经元位置是未知的。确定 细胞外基质（ECM）成分在这些过程中的作用，我们 分析了它们在大脑皮层中的时空分布 老鼠。我们最近的发现是： i) ECM 糖蛋白纤连蛋白 (FN) 沿 放射状胶质细胞穿过前板/底板的过程 神经元； FN 和硫酸软骨素蛋白多糖 (CSPG) 都是 与这些神经元密切相关。这些观察表明 放射状胶质细胞的 ECM 参与神经胶质引导的迁移，并且 围绕前板/亚板神经元的 ECM 是皮质的框架 板块形成。 ii) 到达丘脑传入轴突遵循一条路径 通过含有丰富 CSPG 的底板，表明 CSPG 有助于确定该途径的分子特异性。三） FN 在皮质发育的两个不同阶段产生，首先 由包括放射状胶质细胞在内的神经上皮细胞，然后由 当它们接近并进入皮质时迁移神经元的子集 盘子。检验有关 ECM 功能作用的假设 神经元迁移的组成部分，我们开发了一种器官型 保存胚胎层、放射状胶质细胞和 ECM 成分在无血清培养基中保存数天。神经元分裂 在心室区并迁移到皮质板 制剂，抗体渗透切片。 作为下一阶段的 通过分析，我们将进一步表征特定的细胞外 存在于发育中的视觉皮层的基质成分和 确定哪些细胞产生单独的成分。我们将使用 器官型切片制备以确定哪些细胞表面和 细胞外基质成分在神经元迁移中发挥作用 通过实验扰乱它们的功能。蜂窝的定义 -神经元迁移的分子机制将提供 了解皮质层压异常的基础 这是早期人类大脑受到伤害的常见表现 发展。