Coordinated control of oligodendrocyte development by extrinsic and intrinsic signaling cues

Oligodendrocytes, the myelin-forming cells for axon ensheathment in the central nervous system, are critical for maximizing and maintaining the conduction velocity of nerve impulses and proper brain function. Demyelination caused by injury or disease together with failure of myelin regeneration disrupts the rapid propagation of action potentials along nerve fibers, and is associated with acquired and inherited disorders, including devastating multiple sclerosis and leukodystrophies. The molecular mechanisms of oligodendrocyte myelination and remyelination remain poorly understood. Recently, a series of signaling pathways including Shh, Notch, BMP and Wnt signaling and their intracellular effectors such as Olig1/2, Hes1/5, Smads and TCFs, have been shown to play important roles in regulating oligodendrocyte development and myelination. In this review, we summarize our recent understanding of how these signaling pathways modulate the progression of oligodendrocyte specification and differentiation in a spatiotemporally-specific manner. A better understanding of the complex but coordinated function of extracellular signals and intracellular determinants during oligodendrocyte development will help to devise effective strategies to promote myelin repair for patients with demyelinating diseases.