Cultured neonatal Schwann cells contain and secrete neuregulins.

Neuregulins have become the focus of intense research due to their putative roles in the etiology of certain cancers and to their evolving roles in PNS and CNS development. Evidence has been presented that neuregulins are present in neuronal cells where they act as mediators of neuron-glial signaling. Consistent with this view, we now report that there is a dramatic differential response of Schwann cells to the two major isoforms of neu differentiation factor (NDF alpha and NDF beta). NDF beta is a potent mitogen, whereas NDF alpha is nonmitogenic for Schwann cells. In addition, we report that Schwann cells contain endogenous NDF as well as the mRNA for both isoforms of NDF. Evidence is also presented that several isoforms of NDF are released from cultured Schwann cells. Our data suggest that in addition to functioning as a neuron-glial mediator, endogenous neuregulins may function in an autocrine/paracrine loop or in a juxtacrine- (cell-to-cell) mediated signal between individual Schwann cells or between Schwann cells and neurons.