Schwann cells proliferate but fail to differentiate in defined medium

Primary cultures of dorsal root ganglia cells from 18- to 21-day rodent embryos were studied for their ability to express Schwann cell function in a defined medium lacking serum and embryo extract. It was confirmed that Schwann cells, but not fibroblasts, are able to proliferate in response to contact with axons when cultured in this defined medium. We here report that in this medium, however, differentiation of Schwann cells was arrested before completion of ensheathment and before initiation of myelin formation. Electron microscopic analysis confirmed this ensheathment failure and showed that the extracellular matrix components (basal lamina and thin collagenous fibrils) normally produced by axon-related Schwann cells had not been formed. This absence of extracellular matrix, as well as the presence in the Schwann cell of an increased cytoplasmic granularity (observed in the light microscope) and numerous distended cisterns of rough endoplasmic reticulum, suggest a failure in Schwann cell secretion. However, within one week after addition of serum and embryo extract to the culture medium, the ensheathment failure was corrected and myelination occurred; electron microscopic observations showed the presence of basal lamina and collagen fibrils in association with Schwann cells. These results suggest the presence in serum or embryo extract (or both) of factors necessary for the full expression of Schwann cell function (although a similar requirement is not present for the expression of oligodendrocyte function in culture). We propose that these observations indicate a linkage between Schwann cell secretion and axonal ensheathment, including myelin formation.