A role for insulin-like growth factor-I in the regulation of Schwann cell survival

During postnatal development in the peripheral nerve, differentiating Schwa nn cells are susceptible to apoptotic death. Schwann cell apoptosis is regu lated by axons and serves as one mechanism through which axon and Schwann c ell numbers are correctly matched. This regulation is mediated in part by t he provision of limiting axon-derived trophic molecules, although neureguli n-1 (NRG-1) is the only trophic factor shown to date to support Schwann cel l survival. In this report, we identify insulin-like growth factor-I (IGF-I ) as an additional trophin that can promote Schwann cell survival in vitro. We find that IGF-I, like NRG-1, can prevent the apoptotic death of postnat al rat Schwann cells cultured under conditions of serum withdrawal. Moreove r, we show that differentiating Schwann cells in the rat sciatic nerve expr ess both the IGF-I receptor (IGF-I R) and IGF-I throughout postnatal develo pment. These results indicate that IGF-I is likely to control Schwann cell viability in the developing peripheral nerve and, together with other findi ngs, raise the interesting possibility that such survival regulation may sw itch during postnatal development from an axon-dependent mechanism to an au tocrine and/or paracrine one.