The neuron-glia signal beta-neuregulin promotes Schwann cell motility via the MAPK pathway

Neuregulins constitute a family of related growth factors that play importa nt roles in Schwann cell development and maturation. We investigated the in volvement of beta -neuregulin in Schwann cell migration, using a simple in vitro bioassay. Pure Schwann cells were prepared from the sciatic nerves of 5-day-old rats and were grown in defined medium, with or without serum, un til a monolayer of confluent cells was formed. A cell-free area was then ge nerated by inflicting a scratch resulting in a l-mm-wide gap. Schwann cell migration within the gap was monitored microscopically at given time interv als and was quantified using an image analysis system. The extent of cell p roliferation was estimated by BrdU incorporation, and cell migration was qu antified both in the absence and presence of cytosine arabinoside. We found that, in the absence of serum, beta -neuregulin at a dose submaximal for p roliferation increased the rate of Schwann cell migration by 84%. A more mo derate effect was observed when beta -neuregulin was applied in the presenc e of serum which, however, is by itself responsible for increased Schwann c ell motility. To assess the signal transduction pathways involved in this p rocedure we used one inhibitor of MAPK, PD098059, two inhibitors of PI-3-ki nase, wortmannin, and LY0294002, and three different PKC inhibitors. Of the se PD098059 inhibited the neuregulin-induced enhancement in Schwann cell mi gration by 40%, the two PI-S-kinase inhibitors yielded an approximately 20% inhibition while the PKC inhibitors were ineffective. Our data indicate th at the action of beta -neuregulin on Schwann cell motility is primarily med iated via the MAPK pathway. (C) 2001 Wiley-Liss, Inc.