Intrinsic and extrinsic control of oligodendrocyte development

- Secreted signals regulate OPC specification during development and in the adult.
- OL differentiation is controlled by chromatin remodeling and transcription factors.
- Emerging evidence suggests that OL development is regulated by neuronal activity.
- Knowledge of OL development has informed efforts to generate patient-specific OPCs.
- Understanding OL development will help develop therapies for demyelinating disease.

Oligodendrocytes (OLs) are the myelinating glia of the central nervous system. Myelin is essential for the rapid propagation of action potentials as well as for metabolic support of axons, and its loss in demyelinating diseases like multiple sclerosis has profound pathological consequences. The many steps in the development of OLs - from the specification of oligodendrocyte precursor cells (OPCs) during embryonic development to their differentiation into OLs that myelinate axons - are under tight regulation. Here we discuss recent advances in understanding how these steps of OL development are controlled intrinsically by transcription factors and chromatin remodeling and extrinsically by signaling molecules and neuronal activity. We also discuss how knowledge of these pathways is now allowing us to take steps toward generating patient-specific OPCs for disease modeling and myelin repair.