Oligodendrocytes (OLs) are the myelin-forming cells of the CNS. They derive from progenitor cells that undergo a series of developmental stages to reach the mature myelinating phenotype (Pfeiffer et al., 1993). The progression from progenitor to myelinating oligodendrocyte entails a sequence of events, including cell cycle withdrawal, cytoskeletal changes and synthesis of myelin components. The end-point of differentiation is the formation of myelin sheaths around multiple axons that facilitates saltatory nerve conduction (Franklin, 2002). Although the majority of progenitors develop into oligodendrocytes, some persist in the adult CNS as a population of slowly dividing cells (Ffrench-Constant and Raff, 1986;Wolswijk and Noble, 1989;Reynolds and Hardy, 1997) and are thought to be responsible for remyelination after injury (Gensert and Goldman, 1997;Blakemore and Keirstead, 1999;Chang et al., 2000Chang et al., , 2002;;Franklin, 2002).
Remyelination by progenitor cells requires the recapitulation of a similar sequence of events occurring during development: progenitors proliferate, migrate to the site of lesion, contact the axon, and differentiate into myelinforming cells (Franklin et al., 1997;Franklin, 2002). Given the importance of these events for myelination during normal development and for remyelination after myelin damage, we shall first focus on the extracellular and intracellular signals regulating proliferation and then discuss models proposing a causal relationship between proliferation and differentiation in the oligodendrocyte lineage.