Influence of laminin-2 on Schwann cell-axon interactions.
The dy/dy mouse suffers from a form of muscular dystrophy caused by a substantial reduction in laminin alpha2-chain protein, a major component of both muscle and Schwann cell basal laminae. This article examines the effect of laminin alpha2 deficiency on Schwann cell-axon interactions both in vivo at varying intervals after nerve crush, and in vitro, in cocultures of neurons and Schwann cells. The morphological spectrum of aberrant Schwann cell-axon associations seen in uncrushed dy/dy sciatic nerves was recapitulated during regeneration: myelination of regenerating axons was delayed compared with the process in unaffected mice and the relatively few myelin sheaths which were formed in dy/dy distal nerve stumps were often uncompacted. In vitro, Schwann cells dissociated from adult dy/dy sciatic nerves predictably failed to express detectable laminin alpha2-chain and displayed an unusual multipolar morphology. Branching of neurites, in terms both of numbers of terminal branches and of complexity of branching, from dorsal root ganglia neurons grown on dy/dy Schwann cells, was significantly less extensive than that seen when neurons were cocultured with Schwann cells from unaffected littermates, but this effect was reversed by exogenous laminin-2. Our results lend strong support to the view that laminin-2 is essential for establishing and/or maintaining Schwann cell-axon interactions, in normal and in regenerating nerves.
Uziyel
Y
Y
MRC Centre for Developmental Neurobiology, King's College London, Guy's Campus, London, UK.
Hall
S
S
Cohen
J
J
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D048429:Cell Size / Q000502:physiology; D002478:Cells, Cultured; D007797:Laminin / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009137:Muscular Dystrophy, Animal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009409:Nerve Crush / Q000009:adverse effects; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
D007797:Laminin; C102645:laminin alpha 2