Platelet-derived growth factor-BB supports the survival of cultured rat Schwann cell precursors in synergy with neurotrophin-3

To understand the intimate axon-Schwann cell relationship required for the accurate development and regeneration of the peripheral nervous system (PNS ), it is important to elucidate the repertoire of growth factors involved i n this tightly regulated bi-directional dialogue. We focused on the identif ication and functional characterization of receptor tyrosine kinases (RTKs) in Schwann cells to gain insights into the corresponding growth factor lig ands, which may be regulating the highly controlled differentiation of the Schwann cell lineage. Using an RT-PCR based differential display approach, we have identified 17 tyrosine kinases in embryonic rat sciatic nerves duri ng the crucial transition from Schwann cell precursors to early Schwann cel ls. In this study, we have examined the expression and function of TrkC and the platelet-derived growth factor (PDGF) receptors alpha and beta on Schw ann cell precursor cells. These receptors are expressed on freshly isolated Schwann cell precursors, and we show that PDGF-BB is able to rescue a subp opulation of these cells from apoptotic cell death in vitro. Furthermore, t he TrkC-ligand neurotrophin-3 (NT-3) can act synergistically to potentiate this effect. However, PDGF-BB and NT-3 do not induce Schwann cell precursor proliferation or differentiation. Our data are consistent with a model sug gesting that a combination of growth factors that include PDGF-BB and NT-3 are acting in concert and in synergy to regulate early Schwann cell develop ment. (C) 2000 Wiley-Liss, Inc.