Development and differentiation of Schwann cells.

Using the rat sciatic nerve as a model for the study of Schwann cell differentiation we have identified a Schwann cell precursor, a distinct cell type present in developing nerves at a time when they are projecting to their target tissues. These cells develop into Schwann cells over a relatively short time in vivo. In vitro, they can generate Schwann cells if they are cultured in neuron-conditioned medium or in the presence of neu-differentiation factors (NDF) (neuregulins, heregulins, glial growth factor), a recently discovered family of growth factors expressed at high levels in neurons. Thus neu-differentiation factors may be important neuro-glia signalling molecules in the Schwann cell lineage. Later stages in the development of Schann cells, such as differentiation towards a myelin phenotype, can be studied using cultured Schwann cells. These cells dedifferentiate both in vivo and in vitro when they are deprived of axonal contact. Elevation of intracellular cyclic AMP levels in the absence of cell division causes high levels of expression of Po, the major myelin glycoprotein. TGF beta s and FGFs suppress this induction, while IGFs promote it.