Products of the PLP gene, proteolipid protein and its isoform DM-20, are the most abundant proteins in CNS myelin, and are markers of the oligodendrocyte, the myelin-forming cell in the CNS. The DM-20 transcript has previously been reported to be expressed in newborn oligodendrocyte progenitor cells and during embryonic development. We have therefore used a DM-20 cRNA probe to follow, by in situ hybridization, the oligodendrocyte lineage during embryonic development. DM-20-expressing cells were first detected at E9.5 in the ventricular germinal layer of the laterobasal plate of the diencephalon. At E14.5, DM-20+ cells had largely disappeared from the diencephalic ventricular germinal layer and had colonized the ventral mantle layer at the posterior part of the basal diencephalon. Between E17.5 and P1, the number of DM-20+ cells increased and progressively invaded the major white matter tracts. In the hindbrain, DM-20+ cells appeared at E12.5 in the caudal part of the rhombencephalon, and at E14.5 all along the ventral spinal cord. Between E14.5 and P1, DM-20+ cells progressively colonized, first ventrally then dorsally, all the spinal cord and more extensively the white matter tracts. At E14.5, a large gap separated, rostrally, the medullary columns from the mantle layer cells in the prosencephalon, suggesting that oligodendrocytes in the mid- and forebrain originate from a different pool of precursors than in the rhombencephalon and the spinal cord. Together, these observations suggest that expression of the DM-20 transcript is an early marker of commitment to the oligodendrocyte lineage, and that oligodendrocyte precursors originate in a ventrally restricted region.