Tenascin-C inhibits oligodendrocyte precursor cell migration by both adhesion-dependent and adhesion-independent mechanisms.
Tenascin-C is present within the developing central nervous system during oligodendrocyte precursor cell migration. Tenascin-C is antiadhesive for oligodendrocytes, suggesting a role in controlling the migration of oligodendrocyte precursors and hence the pattern of myelination. Here we show directly that tenascin-C is a repulsive (or antiadhesive) substrate for primary oligodendrocyte precursors and also inhibits their migration. The antimigratory effect of tenascin-C on oligodendroglia is mediated through two distinct mechanisms; reduced substrate adhesion and a direct inhibition of cell migration that is independent of adhesion. These two effects map to different domains of the tenascin-C molecule. The repulsive effect maps to the EGF-like repeats and the alternatively spliced FN III repeats while the direct migration-inhibiting effect maps to FN III repeats 7-8. Our results show tenascin-C to have the novel property of inhibiting migration by both adhesion-dependent and adhesion-independent mechanisms, with different regions of the same molecule responsible for the two effects.
Kiernan
B W
BW
Wellcome Trust and Cancer Research Campaign Institute of Cancer and Developmental Biology, Cambridge, United Kingdom.
Götz
B
B
Faissner
A
A
ffrench-Constant
C
C
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D013234:Stem Cells / Q000502:physiology; D019063:Tenascin / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*
D011994:Recombinant Proteins; D019063:Tenascin