Separate proteolipid protein/DM20 enhancers serve different lineages and stages of development.
DM-20, a product of the proteolipid protein (plp) gene, has been demonstrated in the spinal cord of the mouse embryo as early as embryonic day 12 (E12) in certain cells, some of which are identifiable as oligodendrocyte progenitors. The present work uses optic pathways of rat and mouse as well-characterized systems for the study of gliogenesis. plp gene expression was monitored with a combination of reverse transcriptase polymerase chain reaction, in situ hybridization, and immunostaining with antibodies to different PLP peptide sequences, combined with O-2A lineage markers. In tissue sections, hybridizing cells were detected initially in the proximal optic tracts between E18 and birth and thereafter progressively in the chiasm and optic nerves. Small unbranched cells expressing DM-20 but not myelin basic protein (MBP) and probably representing progenitors were detectable by immunostaining in similar locations. With increasing postnatal ages, cells representing maturing oligodendrocytes which co-label for PLP and MBP are present in the optic pathways. In vitro analysis of freshly dissociated cells from premyelinated optic nerve demonstrated that the plp gene is expressed in some O-2A progenitor cells as well as mature oligodendrocytes. We also present evidence that increase in expression of the plp gene along the O-2A lineage differentiation is not progressive but that downregulation at the proligodendroblast (O4+/O1-) stage probably occurs. We suggest that progenitors express the dm-20 isoform while oligodendrocytes express predominantly the plp isoform. Not all progenitors express the plp gene at the times studied, indicating that the presence of DM-20 is either transitory in individual cells or that only a sub-population is involved. The function of DM-20 at this early stage of the oligodendrocyte lineage has yet to be determined.