EXTRACELLULAR MATRIX AND SCHWANN CELL DIFFERENTIATION

细胞外基质和施万细胞分化

• 批准号: 3400430
• 负责人: CARSON J CORNBROOKS
• 金额: $ 6.63万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1987-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3400430
• 关键词: axon; cell differentiation; extracellular matrix; gel electrophoresis; glia; histochemistry /cytochemistry; immunochemistry; myelination; neural information processing; neurochemistry; peripheral nervous system; tissue /cell culture

The ability of Schwann cells to differentiate and relate to neurons is an extremely important aspect of both normal development and repair of the peripheral nervous system (PNS). A key stage in glial differentiation involves the organization of extracellular matrix (ECM). Whereas numerous ECM molecules are present during the early stages of PNS morphogenesis, the mature basement membranes (basal and reticular laminae) are not organized until the later developmental stages when axons are ensheathed by Schwann cells. The molecular mechanisms involved in matrix formation must be established in order to understand the events controlling PNS development. ECM molecules which remain in the nerve after axotomy are also hypothesized to influence the regeneration of neurons; however, the molecules involved have not been thoroughly studied. Experiments are proposed to examine the disposition of extracellular matrix molecules in vivo in the adult, rat peripheral nerve and in peripheral nerve cells grown in culture. The studies utilize a tissue culture system in which Schwann cells are established in several stages of differentiation and a multidisciplinary approach using immunohistochemical and biochemical techniques is employed to analyse both the synthesis and organization of matrix molecules into intact tissue. In the first set of experiments, antibodies directed against matrix molecules are used to determine the cellular origin and final location of specific antigens associated with Schwann cells before, during and after neuronally induced glial differentiation. Experiment #2 is proposed to test the possibility that Schwann cells in the early stages of differentiation synthesize matrix molecules but do not organize these antigens into intact tissue. Experiment #3 is proposed to study the role of neuronal contact with respect to the synthesis of ECM molecules by Schwann cells. The final experiments (#4) examine the effect of matrix molecules on the morphology, mitotic index and synthetic capabilities of Schwann cells. Data resulting from this proposal addresses the hypothesis that the formation of ECM occurs in a sequential, multistep manner which in turn regulates and is regulated by the differentiation of Schwann cells.

雪旺细胞分化和与神经元相关的能力是一种 无论是正常的发展还是修复都是极其重要的方面 周围神经系统(PNS)。神经胶质细胞分化的关键阶段 涉及细胞外基质(ECM)的组织。鉴于数量众多 细胞外基质分子存在于PNS形态发生的早期阶段， 成熟的基底膜(基底膜和网状膜)没有组织。 直到后来的发育阶段，轴突被Schwann包裹 细胞。涉及基质形成的分子机制必须是 为了了解控制PNS发展的事件而建立的。 神经切断后残留在神经中的细胞外基质分子也被假设。 来影响神经元的再生；然而，涉及的分子 没有得到彻底的研究。建议进行实验，以检验 细胞外基质分子在成年大鼠体内的分布 周围神经和在培养中生长的周围神经细胞。这个 研究利用了一种组织培养系统，其中雪旺细胞 建立了几个阶段的差异化和多学科 方法采用免疫组织化学和生化技术。 分析基质分子的合成和组织 完整的组织。在第一组实验中，抗体直接 抗基质分子用来确定细胞来源和 与雪旺细胞相关的特定抗原的最终位置之前， 在神经诱导的神经胶质分化过程中和之后。实验2 是为了测试雪旺细胞在早期阶段 合成基质分子，但不组织这些 将抗原注入完整的组织。实验3是为了研究这一角色。 神经接触对细胞外基质分子合成的影响 雪旺细胞。最后的实验(#4)检验了基质的影响 分子对细胞形态、有丝分裂指数和合成能力的影响 雪旺细胞。这一提议产生的数据证实了这一假说 ECM的形成是以顺序的、多步骤的方式进行的，在 TURN调控雪旺细胞的分化，并受其调控。