CELL-DEATH IN THE SCHWANN-CELL LINEAGE AND ITS REGULATION BY NEUREGULIN

The development of Schwann cells, the myelin-forming glial cells of th e vertebrate peripheral nervous system, involves a neonatal phase of p roliferation in which cells migrate along and segregate newly formed a xons, Withdrawal from the cell cycle, around postnatal days 2-4 in rod ents, initiates terminal differentiation to the myelinating state, Dur ing this time, Schwann cell number is subject to stringent regulation such that within the first postnatal week, axons and myelinating Schwa nn cells attain the one-to one relationship characteristic of the matu re nerve, The mechanisms that underly this developmental control remai n largely undefined. In this report, we examine the role of apoptosis in the determination of postnatal Schwann cell number, We find that Sc hwann cells isolated from postnatal day 3 rat sciatic nerve undergo ap optosis in vitro upon serum withdrawal and that Schwann cell death can be prevented by beta forms of neuregulin (NRG-beta) but not by fibrob last growth factor 2 or platelet-derived growth factors AA and BB. Thi s NRG-beta-mediated Schwann cell survival is apparently transduced thr ough an ErbBZ/ErbB3 receptor heterodimer. We also provide evidence tha t postnatal Schwann cells undergo developmentally regulated apoptosis in vivo. Together with other recent findings, these results suggest th at Schwann cell apoptosis may play an important role in peripheral ner ve development and that Schwann cell survival may be regulated by acce ss to axonally derived NRG.