EXTRACELLULAR MATRIX AND SCHWANN CELL DIFFERENTIATION

雪旺氏细胞分化和与神经元相关的能力是一个重要因素。 正常发育和修复的一个极其重要的方面， 外周神经系统（PNS）。 胶质细胞分化的关键阶段 涉及细胞外基质（ECM）的组织。 虽然许多 ECM分子存在于PNS形态发生的早期阶段， 成熟的基底膜（基底层和网状层）没有组织 直到发育后期轴突被雪旺氏神经鞘包裹 细胞 参与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。 还假设了轴突切断后保留在神经中的ECM分子 影响神经元的再生;然而， 还没有被彻底研究过。 实验提出了检查 细胞外基质分子在成年大鼠体内的分布 周围神经和培养的周围神经细胞中。 的 研究利用组织培养系统，其中雪旺细胞被 在几个阶段的分化和一个多学科 方法采用免疫组织化学和生物化学技术 分析基质分子的合成和组织， 完整组织 在第一组实验中， 用于确定细胞起源， 与雪旺细胞相关的特异性抗原的最终位置， 在神经元诱导的胶质细胞分化期间和之后。 实验#2 是为了测试雪旺氏细胞在早期阶段 合成基质分子，但不组织这些 抗原注入完整的组织 实验#3旨在研究 的神经元接触方面的ECM分子的合成， 雪旺氏细胞。 最后的实验（#4）检查基质的影响 分子的形态，有丝分裂指数和合成能力， 雪旺氏细胞。 从这一提议中得到的数据解决了这一假设 ECM的形成以连续的多步骤方式发生， turn调节雪旺细胞的分化并受其调节。

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.