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

J Neurosci Res. 2000 Apr 1;60(1):21-36. doi: 10.1002/(SICI)1097-4547(20000401)60:1<21::AID-JNR3>3.0.CO;2-H.

Abstract

Tenascin-R (TN-R), an extracellular matrix constituent of the central nervous system (CNS), has been implicated in a variety of cell-matrix interactions underlying axon growth inhibition/guidance, myelination and neural cell migration during development and regeneration. Although most of the functional analyses have concentrated exclusively on the role of the core protein, the contribution of TN-R glycoconjugates present on many potential sites for N- and O-glycosylation is presently unknown. Here we provide first evidence that TN-R derived from whole rat brain or cultured oligodendrocytes expresses chondroitin sulfate (CS) glycosaminoglycans (GAGs), i.e., C-4S and C-6S, that are recognized by CS-56, a CS/dermatan sulfate-specific monoclonal antibody. Based on different in vitro approaches utilizing substrate-bound glycoprotein, we found that TN-R-linked CS GAGs (1) promote oligodendrocyte migration from white matter microexplants and increase the motility of oligodendrocyte lineage cells; (2) similar to soluble CS GAGs, induce the formation of glial scar-like structures by cultured cerebral astrocytes; and (3) contribute to the antiadhesive properties of TN-R for neuronal cell adhesion in an F3/F11-independent manner, but not to neurite outgrowth inhibition, by mechanism(s) sensitive to chondroitinase or CS-56 treatments. Furthermore, after transection of the postcommissural fornix in adult rat, CS-bearing TN-R was found to be stably upregulated at the lesion site. Our findings 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 astroglial scar formation (CS-dependent) and axon growth inhibition (CS-independent), i.e., suppression of axon regeneration after CNS injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Cell Adhesion Molecules / metabolism*
  • Cell Movement
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / ultrastructure
  • Cerebral Cortex / cytology
  • Chondroitin Sulfates / metabolism*
  • Female
  • Fornix, Brain / physiology
  • Immunohistochemistry
  • In Vitro Techniques
  • Male
  • Mice
  • Nerve Regeneration / physiology
  • Neurites / physiology
  • Oligodendroglia / metabolism*
  • Oligodendroglia / physiology
  • Rats
  • Rats, Wistar
  • Tenascin / metabolism*
  • Up-Regulation

Substances

  • Cell Adhesion Molecules
  • Tenascin
  • tenascin R
  • Chondroitin Sulfates