Signaling axis in Schwann cell proliferation and differentiation

Recent progress in molecular biology has markedly expanded our knowledge of the molecular mechanism behind the proliferation and differentiation processes of Schwann cells, the myelin-forming cells in peripheral nervous systems. Intracellular signaling molecules participate in integrating various stimuli from cytokines and other humoral factors and control the transcriptional activities of the genes that regulate mitosis or differentiation. This article provides an overview of the roles played by the intracellular pathways regulating Schwann cell functions. In Schwann cell proliferation, cyclic adenosine monophosphate signals and mitogen-activated protein kinase pathways play pivotal roles and may also interact with each other. Regarding differentiation, myelin formation is regulated by various cytokines and extracellular matrix molecules. Specifically, platelet-derived growth factor, neuregulin, and insulin-like growth factor-I all are classified as ligands for receptor-type tyrosine kinase and activate common intracellular signaling cascades, mitogen-activated protein kinase pathways, and phosphatidylinositol-3- kinase pathways. The balance of activities between these two pathways appears crucial in regulating Schwann cell differentiation, in which phosphatidylinositol-3-kinase pathways promote myelin formation. Analysis of these signaling molecules hi Schwann cells will enable us not only to understand their physiological development but also to innovate new approaches to treat disorders related to myelination.