Abstract
Oligodendrocytes (OLs) are the myelin-forming cells of the central nervous system (CNS). They differentiate from proliferative OL precursor cells that migrate from the embryonic neuroepithelium throughout the developing CNS before associating with axons and elaborating myelin. Recent research into the regulation of OL differentiation has uncovered a two-stage mechanism of transcriptional control that combines epigenetic repression of transcriptional inhibitors with direct transcriptional activation of myelin genes. This 'two-pronged' approach creates a fail-safe system of genetic control to ensure orderly and unambiguous expression of the myelination program during development and during repair of demyelinated lesions.