Expression of laminin receptors in schwann cell differentiation: evidence for distinct roles.
Schwann cells require laminin-2 throughout nerve development, because mutations in the alpha2 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 alpha6beta1 integrin is expressed before birth, whereas dystroglycan and alpha6beta4 integrin appear perinatally, just before myelination. Although dystroglycan is immediately polarized to the outer surface of Schwann cells, alpha6beta4 appears polarized only after myelination. We showed previously that Schwann cells lacking beta1 integrin do not relate properly to axons before birth. Here we show that the absence of beta1 before birth is not compensated by other laminin receptors, whereas coexpression of both dystroglycan and beta4 integrin is likely required for beta1-null Schwann cells to myelinate after birth. Finally, both beta1-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 beta1-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 beta1 integrins during axonal sorting and by dystroglycan, alpha6beta1, and alpha6beta4 integrins during myelination.
Previtali
Stefano C
SC
Neuropathology Unit, Department of Neuroscience and DIBIT, San Raffaele Scientific Institute, 20132 Milan, Italy.
Nodari
Alessandro
A
Taveggia
Carla
C
Pardini
Celia
C
Dina
Giorgia
G
Villa
Antonello
A
Wrabetz
Lawrence
L
Quattrini
Angelo
A
Feltri
M Laura
ML
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D049030:Dystroglycans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D016023:Integrins / Q000096:biosynthesis; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008815:Mice, Inbred Strains; D008818:Mice, Neurologic Mutants; D009186:Myelin Sheath / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D017933:Peripheral Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017474:Receptors, Laminin / Q000096:biosynthesis*; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D012584:Sciatic Nerve / Q000737:chemistry / Q000378:metabolism
D003598:Cytoskeletal Proteins; D019012:Integrin beta1; D016023:Integrins; D007797:Laminin; D008562:Membrane Glycoproteins; D017474:Receptors, Laminin; D049030:Dystroglycans