TENASCIN-C CONTAINS DISTINCT ADHESIVE, ANTIADHESIVE, AND NEURITE OUTGROWTH-PROMOTING SITES FOR NEURONS

The glia-derived extracellular matrix glycoprotein tenascin-C (TN-C) i s transiently expressed in the developing CNS and may mediate neuron-g lia interactions. Perturbation experiments with specific monoclonal an tibodies suggested that TN-C functions for neural cells are encoded by distinct sites of the glycoprotein (Faissner, A., A. Scholze, and B. Gotz. 1994. Tenascin glycoproteins in developing neural tissues-only d ecoration? Persp. Dev. Neurobiol. 2:53-66). To characterize these furt her, bacterially expressed recombinant domains were generated and used for functional studies. Several short-term-binding sites for mouse CN S neurons could be assigned to the fibronectin type III (FNIII) domain s. Of these, the alternatively spliced insert TNfnA1,2,4,B,D supported initial attachment for both embryonic day 18 (E18) rat and postnatal day 6 (P6) mouse neurons. Only TNfn1-3 supported binding and growth of P6 mouse cerebellar neurons after 24 h, whereas attachment to the oth er domains proved reversible and resulted in cell detachment or aggreg ation. In choice assays on patterned substrates, repulsive properties could be attributed to the EGF-type repeats TNegf, and to TNfnA1,2,4. Finally, neurite outgrowth promoting properties for E18 rat hippocampa l neurons and PO mouse DRG explants could be assigned to TNfnB,D, TNfn D,6, and TNfn6. The epitope of mAb J1/ tn2 which abolishes the neurite outgrowth inducing effect of intact TN-C could be allocated to TNfnD. These observations suggest that TN-C harbors distinct cell-binding, r epulsive? and neurite outgrowth promoting sites for neurons. Furthermo re, the properties of isoform-specific TN-C domains suggest functional significance of the alternative splicing of TN-C glycoproteins.