NEU DIFFERENTIATION FACTOR IS A NEURON-GLIA SIGNAL AND REGULATES SURVIVAL, PROLIFERATION, AND MATURATION OF RAT SCHWANN-CELL PRECURSORS

We show that beta forms of Neu differentiation factor (NDF), homologou s to acetylcholine receptor-inducing activity, glial growth factor, an d heregulin, prevent apoptotic death and stimulate DNA synthesis of th e E14 Schwann cell precursor, an early cell in the rat Schwann cell li neage. When precursors are exposed to NDF in defined medium, they gene rate Schwann cells without the requirement for DNA synthesis and with a time course that is similar to that with which Schwann cells appear in embryonic nerves in vivo. Furthermore, a neuronal signal that also mediates precursor survival and maturation is blocked by the extracell ular domain of the ErbB4 NDF receptor, a protein that specifically blo cks the action of NDFs. These observations provide important evidence that NDF is one of the hitherto elusive neuron-glia signaling molecule s long proposed to regulate development in the Schwann cell lineage.