The long-term goals of this research program are to develop new strategies to promote the proliferation of oligodendrocyte progenitor cells (OLPs) and therapies to enhance remyelination in vivo, which would be of tremendous benefit for patients afflicted with multiple sclerosis (MS) or other demyelinating diseases. Numerous growth and trophic factors have been identified that promote proliferation, differentiation or survival of oligodendrocytes (OLs) and their progenitors. The immediate goal of this project is to define the molecular mechanisms by which specific growth factors promote cell cycle progression in OLPs. The central hypothesis is that growth factors act coordinately to promote the expression and activation of cell cycle regulatory molecules to maximally stimulate OLP proliferation. The specific aims of this proposal are to define the cell cycle kinetics of OLPs following treatment with known mitogens and mitogen combinations, and to define the modulatory roles of cell cycle regulators of the G1-S phase transition during growth factor induced OLP proliferation. Experiments are designed to quantify cell cycle kinetics and cell cycle progression using high-resolution flow cytometric analysis, and to assay changes in expression and activity levels of cell cycle modulatory proteins in growth factor stimulated OLPs using standard protein biochemical analyses.