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The Journal of Neuroscience, July 2, 2003, 23(13):5520-5530

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Expression of Laminin Receptors in Schwann Cell Differentiation: Evidence for Distinct Roles

Stefano C. Previtali,1 Alessandro Nodari,1 Carla Taveggia,1 Celia Pardini,1 Giorgia Dina,1 Antonello Villa,2 Lawrence Wrabetz,1 Angelo Quattrini,1 and M. Laura Feltri1

1Neuropathology Unit, Department of Neuroscience and DIBIT, San Raffaele Scientific Institute, 20132 Milan, Italy, and 2Consorzio MIA-DNTR University MI-Bicocca, 20126 Milan, Italy

Schwann cells require laminin-2 throughout nerve development, because mutations in the {alpha}2 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 {alpha}6{beta}1 integrin is expressed before birth, whereas dystroglycan and {alpha}6{beta}4 integrin appear perinatally, just before myelination. Although dystroglycan is immediately polarized to the outer surface of Schwann cells,{alpha}6{beta}4 appears polarized only after myelination. We showed previously that Schwann cells lacking {beta}1 integrin do not relate properly to axons before birth. Here we show that the absence of {beta}1 before birth is not compensated by other laminin receptors, whereas coexpression of both dystroglycan and {beta}4 integrin is likely required for {beta}1-null Schwann cells to myelinate after birth. Finally, both {beta}1-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 {beta}1-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 {beta}1 integrins during axonal sorting and by dystroglycan, {alpha}6{beta}1, and {alpha}6{beta}4 integrins during myelination.

Key words: laminin receptors; Schwann cells; dystrophic mice; integrins; dystroglycan; myelination; adhesion

Received Jul. 22, 2002; revised Apr. 9, 2003; accepted Apr. 14, 2003.




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