CAMP-INDUCED MORPHOLOGICAL-CHANGES IN AN IMMORTALIZED SCHWANN-CELL LINE - A PRELUDE TO DIFFERENTIATION

Schwann cells (SC), the myelinating cells of the peripheral nervous sy stem, show a remarkable capacity to switch from a differentiated state to a proliferative state both during development and peripheral nerve regeneration. In order to better understand the regulatory mechanisms involved with this change we are studying a Schwann cell line transfe cted with the SV-40 large T gene (TSC). Serum-free medium combined wit h elevating intra-cellular cAMP levels produced a slower proliferating TSC whose morphology changed from pleiomorphic to process bearing, re miniscent of primary SC in culture. This change was abrogated by colce mid but was unaltered by cytochalasin D, indicating a major role for m icrotubules. Ultrastructural studies demonstrated numerous microtubule s in the cellular extensions which correlated with strong immunocytoch emical staining for tubulin in the processes. Analysis of cytoskeletal fractions from the treated cells revealed a greater proportion of tub ulin in the polymerized state compared with untreated cells which clos ely resembled the distribution in primary SC. The cytoskeletal changes observed in the TSC as a result of elevating the intra-cellular cAMP levels may reflect the earliest cellular changes in the induction of m yelination. (C) 1994 Wiley-Liss, Inc.