Regulation of the production and proliferation of oligodendrocyte progenitors in development and injury

Oligodendrocytes are abundant cells in the central nervous system (CNS) with the important dual role of increasing the speed of action potential conduction by myelinating axons and providing metabolic support for the axons they ensheath. They are damaged in multiple diseases including Multiple Sclerosis and families of leukodystrophies and their replacement in injury and disease is an area of great interest. Oligodendrocytes are produced from a lineage-restricted oligodendrocyte progenitor cells (OPCs). OPCs are distributed throughout the CNS and are of interest, both as the source of oligodendrocytes, and as potential synaptic signaling partners with neurons. Little is known about the signals that control the production of OPCs from neural progenitor cells during development or the signals that regulate OPC proliferation and the maintenance of a pool of OPCs in the nervous system throughout life. For my thesis work I have shown that the canonical Wnt pathway inhibits the production of OPCs from intermediate progenitor cells and a decrease in Wnt signaling is necessary to allow OPC production. I have also shown that Suppressor of Fused (Sufu), a direct target of SoxE transcription factor regulation, is an inhibitor of OPC proliferation and that decreasing Sufu expression in the CNS increases the number of OPCs found in the CNS during development and in a demyelinating lesion at adult ages. My findings shed new light on the regulation of these early steps in the oligodendrocyte lineage