Developing Schwann cells acquire the ability to survive without axons by establishing an autocrine circuit involving insulin-like growth factor, neurotrophin-3, and platelet-derived growth factor-BB

Although Schwann cell precursors from early embryonic nerves die in the abs ence of axonal signals, Schwann cells in older nerves can survive in the ab sence of axons in the distal stump of transected nerves. This is crucially important, because successful axonal regrowth in a damaged nerve depends on interactions with living Schwann cells in the denervated distal stump. Her e we show that Schwann cells acquire the ability to survive without axons b y establishing an autocrine survival loop. This mechanism is absent in prec ursors. We show that insulin-like growth factor, neurotrophin-3, and platel et-derived growth factor-BE are important components of this autocrine surv ival signal. The secretion of these factors by Schwann cells has significan t implications for cellular communication in developing nerves, in view of their known ability to regulate survival and differentiation of other cells including neurons.