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

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.

Neural Tissue Co-Culture with Mesenchyme to Investigate Patterningof Peripheral Nerve During Murine Embryonic Limb Development

“…There are several possibilities with regard to versican function as a barrier molecule to axonal growth that could faciltitae neuronal patterning in the developing limb. The lectin domain of versican binds tenascin (Aspberg et al 1995), increasing tenascin's anti-adhesive properties (Probstmeier et al 2000). Likewise, versican binding to other ECM molecules may block neurite adhesion to other permissive matrix substrates such as fibronectin and collagen (Yamagata et al 1989), which, along with versican, are all expressed in incipient limb cartilage tissues (Shinomura et al 1990).…”

Repulsive guidance of axons of spinal sensory neurons in Xenopus laevis embryos: Roles of Contactin and notochord‐derived chondroitin sulfate proteoglycans

“…This repulsive response of mouse DRG neurons can be blocked by addition of anti-Contactin antibody to the culture medium (Xiao et al 1998). However, the involvement of the CS side chains of tenascin-R has not been confirmed in this Contactin-mediated axonal repulsion (Probstmeier et al 2000). Contactin has also been shown to interact with phosphacans, major extracellular matrix CSPG in the central nervous system that are formed by alternative RNA splicing of the RPTPβ/PTPζ transcript (Peles et al 1995).…”

“…2000). CSPG expression is reportedly increased at the site of nervous tissue injury, and this may signal to regenerating axons the repulsive guidance cue (Probstmeier et al . 2000; Becker et al .…”

“…1998). However, the involvement of the CS side chains of tenascin‐R has not been confirmed in this Contactin‐mediated axonal repulsion (Probstmeier et al . 2000).…”

“…This CSPG distribution may also regulate the migrating pathways of neural crest cells (Perissinotto et al 2000). CSPG expression is reportedly increased at the site of nervous tissue injury, and this may signal to regenerating axons the repulsive guidance cue (Probstmeier et al 2000;Becker et al 2004). A recent study (Kantor et al 2004) also suggests that CSPG can bind to other signal molecules presented on cell surface or extracellular matrix and modify their axon guidance cues.…”