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

神经胶质细胞对中枢和周围神经系统的正常功能都是必不可少的。事实上，许多神经系统疾病都是由于这类细胞功能不正常所致。此外，这些细胞的异常生长导致了最常见类型的神经系统癌症。在许多细胞类型中，了解有丝分裂生长因子受体使用的信号通路对于了解细胞的疾病状态至关重要。PDGF作为一种有效的胶质细胞有丝分裂原。在雪旺细胞的情况下，PDGF的作用被Forskolin增强，Forskolin是cAMP途径的激活剂。本课题旨在研究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Forskolin如何补充PDGF的作用。其次，我们将确定哪些已知的PDGF受体信号传导元件在该系统中是必需的。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.