Differentiation-specific regulation of Schwann cell expression of the major myelin glycoprotein

Previous experiments demonstrated that Schwann cells from permanently transected sciatic nerves of adult rats synthesize basal levels of the major myelin glycoprotein (P₀). This denervated preparation at 35 days after transection was characterized by the absence of both axons and myelin assembly. The present investigation demonstrates that production of P₀ continues after culture of the Schwann cells as endoneurial slices for 14 days. Thus, the level of differentiation is unchanged in culture even though only basal levels of P₀ are produced and post-translational processing is complete. In contrast, Schwann cells from 4-day-old rat sciatic nerves actively synthesized P₀ and assembled myelin membrane; however, after only 4 days in culture of biosynthesis of P₀ ceased. Because the same culture conditions and precursor incorporation procedures were used for both neonatal and transected nerves, it is proposed that neonatal Schwann cells in culture return to a progenitor state that is not capable of P₀ gene expression. This comparison, both before and after culture, of neonatal Schwann cells that are programmed to myelinate and Schwann cells from the adult transected nerve that were in a myelin-maintaining mode provides a useful model for investigating the mechanisms by which differential gene expression is controlled. These results confirm that axons are not necessary for specifying P₀ gene expression by Schwann cells from the adult transected nerves. The role that axons play in controlling P₀ gene expression by neonatal Schwann cells in culture, however, has yet to be determined. It is concluded that the differentiation and maturation of Schwann cells is a multistage process that allows the sequential production of specific gene products.