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

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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.