EXPRESSION OF PROTEOLIPID PROTEIN GENE IS DIRECTLY ASSOCIATED WITH SECRETION OF A FACTOR INFLUENCING OLIGODENDROCYTE DEVELOPMENT

Oligodendroglial cell death in the myelin proteolipid protein (PLP) mu tants can be partially rescued by the environment factor(s) supplied b y the wild-type cells in vivo and in vitro. It is possible that the pr esence of PLP or DM-20 results in secretion of a factor or factors in the CNS influencing oligodendrocyte development. We previously showed that DM-20 mRNA is produced in G26 mouse oligodendroglioma, B104 rat n euroblastoma, and B16 mouse melanoma but not in NIH3T3 mouse fibroblas t cell lines. Culture supernatants from these cell lines were added to primary glial cell cultures from embryonic day 17 mouse brain, After 4 days, the number of oligodendrocytes present in cultures with supern atants from DM-20-producing cells (G26, B104, and B16) was significant ly higher than that of control cultures but not with the NIH3T3 supern atant. To investigate more directly whether the PLP gene expression is involved in this process, NIH3T3 cells (nonneural cells) were forced to produce PLP or DM-20, By addition of the supernatants from the PLP/ DM-20 transformants, the number of oligodendrocytes in the mixed glial cell cultures increased. This clearly demonstrates that the expressio n of the PLP gene is sufficient for and directly associated with secre tion of a factor, which influences the oligodendrocyte development.