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

Abstract

Although Schwann cell precursors from early embryonic nerves die in the absence of axonal signals, Schwann cells in older nerves can survive in the absence 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. Here we show that Schwann cells acquire the ability to survive without axons by establishing an autocrine survival loop. This mechanism is absent in precursors. We show that insulin-like growth factor, neurotrophin-3, and platelet-derived growth factor-BB are important components of this autocrine survival signal. The secretion of these factors by Schwann cells has significant implications for cellular communication in developing nerves, in view of their known ability to regulate survival and differentiation of other cells including neurons.

Schwann cell proliferation during Wallerian degeneration is not necessary for regeneration and remyelination of the peripheral nerves: Axon-dependent removal of newly generated Schwann cells by apoptosis

“…Unlike Schwann cell precursors (S100 − ), S100 + Schwann cells survive in culture in the absence of axonal contact owing to the autocrine loop (Cheng et al 1998;Dowsing et al 1999;Meier et al 1999). However, our data indicates that the S100 + cells found in adult PNS following nerve injury are susceptible to death in the absence of axonal contact.…”

The Low-Density Lipoprotein Receptor-Related Protein Is a Pro-Survival Receptor in Schwann Cells: Possible Implications in Peripheral Nerve Injury

“…Survival of adult Schwann cells depends on autocrine signaling circuits, involving factors such as PDGF, neurotrophin-3, and IGF-II (Meier et al, 1999). Because LRP-1 is a multifunctional receptor (Strickland et al, 2002;Gonias et al, 2004), binding numerous ligands generated at injury sites and controlling diverse cell-signaling pathways, we initiated experiments to determine whether LRP-1 regulates the response to peripheral nerve injury.…”

“…In the adult rat, sciatic nerve axotomy does not induce Schwann cell death (Grinspan et al, 1996). Implicated autocrine survival factors include platelet-derived growth factor (PDGF), neurotrophin-3, and insulin-like growth factor-II (Meier et al, 1999).…”

Glial cells: Old cells with new twists

“…Mature SCs can survive in the absence of neurons, whereas immature SCs depend on axonal signals (Jessen and Mirsky, 2005). Mature SCs are able to block apoptosis by participating in an autocrine circuit by releasing growth factors, including insulin-like growth factors (Cheng et al, 2000), platelet derived growth factor-BB (PDGF-BB) (Eccleston et al, 1990) and neurotrophin-3 (NT-3) (Bhatheja and Field, 2006;Britsch et al, 2001;Meier et al, 1999;Porter et al, 1987). This autocrine circuit is not seen in precursor or immature SCs (Jessen and Mirsky, 2005).…”