The plp gene encodes the proteolipid protein and its alternatively spliced product DM-20, major proteins of CNS myelin. In the mouse, plp/dm-20 transcripts are expressed beginning at embryonic day 9.5 (E9.5) by restricted foci of germinative neuroepithelial cells. To determine the identity of the neural precursors expressing plp/dm-20, a zeomycin resistance gene fused to the lacZ reporter was expressed in transgenic mice under the control of the plp regulatory sequences. In the three different lines generated, the pattern of ␤-galactosidase expression was similar and superimposable on the expression pattern of endogenous plp/dm-20. Both in vivo and in vitro, the transgene was expressed by O4 ϩ pre-oligodendrocytes, and later by RIP ϩ differentiated oligodendrocytes, but not by neuronal cells, astrocytes, or radial glial cells. After zeomycin selection, a dramatic enrichment in O4 ϩ pre-oligodendrocytes was observed in cultures derived from E12.5 transgenic embryos. This enrichment indicates the oligodendroglial specification of neural precursors that continuously express plp/dm-20. Early plp/dm-20-expressing precursors, however, appear to be a separate population from previously described PDGFR␣ oligodendrocyte precursors, as shown by the striking differences in their (1) patterns of distribution and (2) responsiveness to PDGF. These data suggest that oligodendrocytes have a plural origin and that early plp/dm-20 defines one of the neural lineages generating oligodendrocytes.

Oligodendrocytes are the myelin-forming cells in the central nervous system of vertebrates. In the rodent embryo, these cells have been shown to emerge from restricted territories of the neuroepithelium. However, a comprehensive view of the development of oligodendroglial populations from their ventricular sources remains to be established. As a first step toward this aim, we have examined in vivo the spatiotemporal emergence of oligodendrocytes in the chick embryonic brain. We have detailed the patterns of expression of three early markers of the oligodendroglial lineage: the plp/dm-20 and PDGFRalpha transcripts and the O4-reactive antigen. During embryonic development, these molecules showed a similar segmental pattern of expression. However, plp/dm-20(+) cells were already observed, in the ventricular layer, at E2.5, i.e., 2 days before the appearance of O4(+) and PDGFRalpha(+) cells, suggesting that oligodendrocyte precursors arise nearly simultaneously with neurons. In the chick embryonic brain, the onset of expression of plp/dm-20 appears therefore to be the earliest event indicative of oligodendroglial specification and we propose, based on the expression of plp/dm-20 transcript, a ventricular map of the foci at which oligodendrocytes originate. In addition, we document the precocious segregation, from E5, of plp/dm-20(+) and PDGFRalpha(+) oligodendroglial cells in the subventricular and mantle layers of the brain.

The plp gene encodes the proteolipid protein and its alternatively spliced product DM-20, major proteins of CNS myelin. In the mouse, plp/dm-20 transcripts are expressed beginning at embryonic day 9.5 (E9.5) by restricted foci of germinative neuroepithelial cells. To determine the identity of the neural precursors expressing plp/dm-20, a zeomycin resistance gene fused to the lacZ reporter was expressed in transgenic mice under the control of the plp regulatory sequences. In the three different lines generated, the pattern of ␤-galactosidase expression was similar and superimposable on the expression pattern of endogenous plp/dm-20. Both in vivo and in vitro, the transgene was expressed by O4 ϩ pre-oligodendrocytes, and later by RIP ϩ differentiated oligodendrocytes, but not by neuronal cells, astrocytes, or radial glial cells. After zeomycin selection, a dramatic enrichment in O4 ϩ pre-oligodendrocytes was observed in cultures derived from E12.5 transgenic embryos. This enrichment indicates the oligodendroglial specification of neural precursors that continuously express plp/dm-20. Early plp/dm-20-expressing precursors, however, appear to be a separate population from previously described PDGFR␣ oligodendrocyte precursors, as shown by the striking differences in their (1) patterns of distribution and (2) responsiveness to PDGF. These data suggest that oligodendrocytes have a plural origin and that early plp/dm-20 defines one of the neural lineages generating oligodendrocytes.