NEURON-MATRIX INTERACTIONS IN DEVELOPMENT & REGENERATION

发育中的神经元-基质相互作用

• 批准号: 3408965
• 负责人: PAUL C. LETOURNEAU
• 金额: $ 15.25万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1990-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3408965
• 关键词: Schwann cells; affinity chromatography; axon; basement membrane; cell adhesion; cell cell interaction; central nervous system; extracellular matrix; glia; glycoproteins; immunochemistry; laboratory mouse; laboratory rabbit; laboratory rat; laminin; membrane proteins; mucopolysaccharides; nervous system regeneration; neurogenesis; neurons; peripheral nervous system; radioassay; receptor

Development and regeneration of the nervous system involve a complex set of interactions between cell types (neurons, glia, Schwann cells), and between cells and extracellular matrix materials such as glycoproteins and glycosaminoglycans. Only a few of the molecules on the surfaces of nervous system cell that are involved in these interactions have been identified. The importance of extracellular matrix molecules in nerve development is just now being recognized. One extracellular matrix molecule that be important is laminin, a basement membrane glycoprotein. Laminin is found in peripheral nerves, and is also transiently seen in the brain during development and following injury. Laminin promotes rapid neurite elongation from CNS and PNS neurons. It is synthesized by Schwann cells and may be important in their differentiation. The specific aims of this grant proposal are to examine more closely the interactions between neurons, glia, and Schwann cells with fragments of laminin in order to identify regions of laminin important for cell- laminin interactions; to isolate molecules from the surfaces of neural and glial cells that are involved in the cell-laminin interactions; to make monoclonal and polyclonal antibodies to these cell surface laminin-binding molecules; and, to test the effects of the antibodies against laminin-binding molecules on neuron-laminin and neuron-glial cell interactions, as well as neurite elongation on laminin. Laminin fragments will be used in cell adhesion and neurite outgrowth studies to identify important subregions of the molecule. Laminin binding molecules will be isolated from neural and glial cells by laminin affinity chromatography, and will be used to produce polyclonal and monoclonal antibodies. The antibodies will be tested for the ability to block neuron-laminin and glial-laminin interactions in cell adhesion and radioreceptor assays. The antibodies will also be tested for the ability to interfere with neurite elongation on laminin, and neuron-glial cell interactions. One long term goal of these studies is to identify differences between CNS and PNS that prevent but not develop methods to manipulate brain and spinal cord tissue to allow repair and regeneration following injury.

神经系统的发育和再生涉及 细胞类型（神经元、神经胶质细胞、 施万细胞）以及细胞和细胞外基质之间 糖蛋白和糖胺聚糖等物质。 只有一个 神经系统细胞表面的分子很少 参与这些相互作用的人员已被确定。 这 细胞外基质分子在神经中的重要性 发展现在才被认识到。 一种细胞外 重要的基质分子是层粘连蛋白，一种基底 膜糖蛋白。 层粘连蛋白存在于周围神经中， 并且在发育和发育过程中也会短暂地出现在大脑中 受伤后。 层粘连蛋白促进神经突快速伸长 CNS 和 PNS 神经元。 它是由雪旺细胞合成的，可能 对他们的差异化很重要。 本次活动的具体目标 拨款提案将更仔细地研究相互作用 神经元、神经胶质细胞和雪旺细胞之间的碎片 层粘连蛋白，以识别对细胞重要的层粘连蛋白区域 层粘连蛋白相互作用；将分子从表面分离 参与细胞层粘连蛋白的神经细胞和神经胶质细胞 互动；制备单克隆和多克隆抗体 这些细胞表面层粘连蛋白结合分子；并且，为了测试 抗层粘连蛋白结合分子的抗体对 神经元-层粘连蛋白和神经元-胶质细胞相互作用，以及 层粘连蛋白上的神经突伸长。 层粘连蛋白片段将用于 细胞粘附和神经突生长研究以确定重要的 分子的子区域。 层粘连蛋白结合分子将是 通过层粘连蛋白亲和力从神经细胞和神经胶质细胞中分离出来 色谱法，并将用于生产多克隆和 单克隆抗体。 抗体将被测试 阻断神经元-层粘连蛋白和神经胶质-层粘连蛋白相互作用的能力 细胞粘附和放射受体测定。 抗体也会 测试干扰神经突伸长的能力 层粘连蛋白和神经元-胶质细胞相互作用。 一项长期目标是 这些研究旨在确定 CNS 和 PNS 之间的差异 预防但不开发操纵大脑和脊髓的方法 脊髓组织在受伤后可以修复和再生。