expression of Nkx6.1/Nkx6.2 coordinate expression of Olig1 and Olig2 in neuroepithelial cells of the pMN and p3 domains of the ventral ventricular zone. Together, Nkx2.2 and Olig1/Olig2 drive OPC specification. In the forebrain, three regionally distinct sources have been shown to generate OPCs sequentially. OPCs first originate from Nkx2.1-expressing cells in the ventricular zone of the medial ganglionic eminence. Some OPCs are also generated from multipotent progenitors in the subventricular zone (SVZ). These cells migrate into the olfactory bulb. Depending on their origin in the SVZ, these progenitors give rise to either OPCs or astrocytes. Typically, cells originating from the posterior and dorsomedial SVZ produce more oligodendrocytes owing to increased exposure to posterior Shh signaling and dorsal Wnt signaling which favors OPC specification, in contrast to ventral Bmp signaling which inhibits it. As development progresses, second and third waves of OPCs originate from Gsh2-expressing cells in the lateral and caudal ganglionic eminences and generate the majority of adult oligodendrocytes. After the committed progenitor cells exit the germinal zones, they migrate and proliferate locally to eventually occupy the entire CNS parenchyma. OPCs are highly proliferative, migratory, and have bipolar morphology. OPCs continue to exist in in both white and gray matter in the adult brain and maintain their population through self-renewal. White matter OPCs proliferate at higher rates and are best known for their contributions to adult myelinogenesis, while gray matter OPCs are slowly proliferative or quiescent and mostly remain in an immature state. Subpopulations of OPCs have different resting membrane potentials, ion channel expression, and ability to generate action potentials. Fate Typically beginning in postnatal development, OPCs myelinate the entire central nervous system (CNS). They differentiate into the less mobile preoligodendrocytes that further differentiate into oligodendrocytes, a process characterized by the emergence of the expression of myelin basic protein (MBP), proteolipid protein (PLP), or myelin-associated glycoprotein (MAG). Following terminal differentiation in vivo, mature oligodendrocytes wrap around and myelinate axons. In vitro, oligodendrocytes create an extensive network of myelin-like sheets. The process of differentiation can be observed both through morphological changes and cell surface markers specific to the discrete stage of differentiation, though the signals for differentiation are unknown. The various waves of OPCs could myelinate distinct regions of the brain, which suggests that distinct functional subpopulations of OPCs perform different functions. Differentiation of OPCs into oligodendrocytes involves massive reorganization of cytoskeleton proteins ultimately resulting in increased cell branching and lamella