Tenascin-R interferes with integrin-dependent oligodendrocyte precursor cell adhesion by a ganglioside-mediated...

Oligodendrocyte (OL) lineage progression is characterized by the transient expression of the disialoganglioside GD3 by OL precursor (preOL) cells followed by the sequential expression of myelin-specific lipids and proteins. Whereas GD3+ preOLs are highly motile cells, the migratory capacity of OLs committed to terminal differentiation is strongly reduced, and we have recently shown that the extracellular matrix protein tenascin-R (TN-R) promotes the stable adhesion and differentiation of O4+ OLs by a sulphatide-mediated autocrine mechanism (O4 is a monoclonal antibody recognizing sulphatides/seminolipids expressed by OLs and in myelin). Using culture conditions that allow the isolation of mouse OLs at distinct lineage stages, here we demonstrate that TN-R is antiadhesive for GD3+ preOLs and inhibits their integrin-dependent adhesion to fibronectin (FN) by a disialoganglioside-mediated signalling mechanism affecting the tyrosine phosphorylation of the focal adhesion kinase. This responsive mechanism appears to be common to various cell types expressing disialogangliosides as: (i) disialogangliosides interfered with the inhibition of cell adhesion of different neural and non-neural cells on substrata containing TN-R and FN or RGD-containing FN fragments. TN-R interacted specifically with disialoganglioside-expressing cells or immobilized gangliosides, and ganglioside treatment of TN-R substrata resulted in a delayed preOL cell detachment as a function of time. We conclude that OL response to one and the same signal in the extracellular matrix critically depends on the molecular repertoire expressed by OLs at different lineage stages and could thus define their final positioning.