Proteolipid protein gene product can be secreted and exhibit biological activity during early development

A gene encoding myelin proteolipid protein (PLP) and its smaller isoform DM 20 is expressed at least 1 week before myelination. Mutations within the ge ne cause abnormalities in the development of premyelinating oligodendrocyte s, resulting in hypomyelinating disorders. These findings suggest a premyel inating function of the PLP gene products. We previously demonstrated that PLP gene expression is directly associated with secretion of a factor that increases the number of oligodendrocytes. Here we show that this activity i s mediated by a secreted fragment containing the G-terminal portion of PLP. This factor increased the bromodeoxyuridine incorporation rate in both oli godendrocyte and astrocyte lineage cells; a synthetic peptide (PLP 215-232) exhibited a similar activity. Dose-response curves of PLP and PLP peptide showed maximum activities at a concentration in the picomolar range, which decreased at higher concentrations. These observations demonstrate that a s ecreted PLP gene product exerts biological activity at a premyelinating sta ge before the major induction of the gene.