Expression of laminin receptors in Schwann cell differentiation: Evidence for distinct roles

Abstract

Schwann cells require laminin-2 throughout nerve development, because mutations in the α2 chain in dystrophic mice interfere with sorting of axons before birth and formation of myelin internodes after birth. Mature Schwann cells express several laminin receptors, but their expression and roles in development are poorly understood. Therefore, we correlated the onset of myelination in nerve and synchronized myelinating cultures to the appearance of integrins and dystroglycan in Schwann cells. Only α6β1 integrin is expressed before birth, whereas dystroglycan and α6β4 integrin appear perinatally, just before myelination. Although dystroglycan is immediately polarized to the outer surface of Schwann cells, α6β4 appears polarized only after myelination. We showed previously that Schwann cells lacking β1 integrin do not relate properly to axons before birth. Here we show that the absence of β1 before birth is not compensated by other laminin receptors, whereas coexpression of both dystroglycan and β4 integrin is likely required for β1-null Schwann cells to myelinate after birth. Finally, both β1-null and dystrophic nerves contain bundles of unsorted axons, but they are predominant in different regions: in spinal roots in dystrophic mice and in nerves in β1-null mice. We show that differential compensation by laminin-1, but not laminin receptors may partially explain this. These data suggest that the action of laminin is mediated by β1 integrins during axonal sorting and by dystroglycan, α6β1, and α6β4 integrins during myelination.