MOLECULAR MECHANISMS OF PDGF SIGNALING --GROWTH & DEVELOPMENT OF SCHWANN CELLS

神经胶质细胞对于中枢和外周神经系统的正常功能都是必不可少的。许多神经系统疾病实际上是由于这种细胞的功能不正常。此外，这些细胞的异常生长导致最常见的神经系统癌症类型。在许多细胞类型中，有丝分裂生长因子受体所使用的信号通路的理解已被证明是理解细胞的疾病状态所必需的。PDGF作为神经胶质细胞的有效促分裂剂。在雪旺氏细胞的情况下，PDGF的作用被毛喉素（cAMP途径的激活剂）增强。本研究旨在探讨PDGF诱导雪旺细胞生长的信号通路。将获得三种类型的信息。首先，我们将确定毛喉素如何补充PDGF的作用。其次，我们将确定在这个系统中需要哪些已知的PDGF受体信号传导元件。最后，我们将使用涉及基因敲除技术的小鼠模型系统来测试我们的发现与体内雪旺细胞正常和异常生长的相关性。

Glial cells are essential for the proper function of both the central and peripheral nervous system. Many diseases of the nervous system are in fact due to improper function of this cell class. Moreover the aberrant growth of these cells leads to the most common types of cancers of the nervous system. In many cell types an understanding of the signalling pathways used by receptors for mitogenic growth factors has proved essential to understanding the disease states of the cells. PDGF acts as a potent mitogen for glial cells. In the case of Schwann cells the action of PDGF is potentiated by Forskolin, an activator of the cAMP pathway. This proposal aims to study the signaling pathways involved in PDGF induced growth of Schwann cells. Three types of information will be obtained. First we will determine how Forskolin complements the action of PDGF. Second we will determine which of the known elements of PDGF receptor signaling are required in this system. Finally we will use mouse model systems involving gene knockout technology to test the relevance of our findings to the normal and abnormal growth of Schwann cells in vivo.