DIVISION-OF-LABOR OF SCHWANN-CELL INTEGRINS DURING MIGRATION ON PERIPHERAL-NERVE EXTRACELLULAR-MATRIX LIGANDS

Myelination of the peripheral nervous system (PNS) requires the migrat ion of Schwann cells during both development and regeneration. We have characterized the expression pattern of Schwann cell integrins and an alyzed their role in migration on different ECM substrates known to be present within the PNS. We found that Schwann cells in cell culture e xpress four beta 1 integrins, alpha 1 beta 1, alpha 2 beta 1, alpha 6 beta 1, and another unidentified beta 1 integrin, as well as two alpha v integrins, alpha v beta 3 and alpha v beta 8. Using the Varani migr ation assay, we found that laminin-l, laminin-2 (merosin), and fibrone ctin increased Schwann cell migration, while vitronectin and collagen did not increase migration compared to an uncoated plastic substrate. Schwann cell migration on laminin-l and laminin-2 (merosin) was blocke d by antibodies against beta 1 integrins, but not affected by RGD pept ides or antibodies against beta 3 integrins. In contrast, migration on fibronectin was unaffected by antibodies against beta 1 and beta 3 in tegrins but was blocked by RGD peptides. This in vitro study shows tha t there is a division of labor of Schwann cell integrins in the regula tion of migration on peripheral nerve ECM components; beta 1 integrins mediate migration on laminin-1 and laminin-2 (merosin), while alpha v integrins mediate migration on fibronectin. Taken together, these res ults suggest that multiple interactions between Schwann cell integrins and ECM within the PNS will contribute to Schwann cell migration duri ng myelination of the PNS. (C) 1997 Academic Press.