Chondroitin sulfates expressed on oligodendrocyte-derived tenascin-R are involved in neural cell recognition. Functional implications during CNS development and regeneration

Tenascin-R (TN-R), an extracellular matrix constituent of the central nervo us system (CNS), has been implicated in a variety of cell-matrix interactio ns underlying axon growth inhibition/guidance, myelination and neural cell migration during development and regeneration. Although most of the functio nal analyses have concentrated exclusively on the role of the core protein, the contribution of tN-R glycoconjugates present on many potential sites f or N- and O-glycosylation is presently unknown. Here we provide first evide nce that TN-R derived from whole rat brain or cultured oligodendrocytes exp resses chondroitin sulfate (CS) glycosaminoglycans (GAGs), i,e., C-4S and C -6S, that are recognized by CS-56, a CS/dermatan sulfate-specific monoclona l antibody. Based on different in vitro approaches utilizing substrate-boun d glycoprotein, we found that TN-R-linked CS GAGs (1) promote oligodendrocy te migration from white matter microexplants and increase the motility of o ligodendrocyte lineage cells; (2) similar to soluble CS GAGs, induce the fo rmation of glial scar-like structures by cultured cerebral astrocytes; and (3) contribute to the antiadhesive properties of TN-R for neuronal cell adh esion in an F3/F11-independent manner, but not to neurite outgrowth inhibit ion, by mechanism(s) sensitive to chondroitinase or CS-56 treatments. Furth ermore, after transection of the postcommissural fornix in adult rat, CS-be aring TN-R was found to be stably upregulated at the lesion site. Our findi ngs suggest the functional impact of TN-R-linked CS on neural cell adhesion and migration during brain morphogenesis and the contribution of TN-R to a stroglial scar formation (CS-dependent) and axon growth inhibition (CS-inde pendent), i,e,, suppression of axon regeneration after CNS injury. J. Neuro sci. Res. 60:21-36, 2000. (C) 2000 Wiley-Liss, Inc.