Long and short splice variants of human tenascin differentially regulate neurite outgrowth

Tenascin-C has been implicated in regulation of neurite outgrowth both during development and after injury; however, its role as permissive vs inhibitory remains controversial. We report that different tenascin splice variants may have dramatically different impacts on neuronal growth. In a cell culture model, the largest and smallest splice variants (TN.L and TN.S) of human tenascin both promoted process extension when surface-bound. In contrast, soluble TN.S inhibited outgrowth, whereas soluble TN.L had no inhibitory effect. Perturbation experiments with antibodies, and outgrowth experiments with recombinant tenascin fragments, indicate that the differential properties of these molecules can be attributed to their distinctive array of FN-III repeats. Monoclonal antibodies were used to demonstrate at least two distinct neurite outgrowth promoting domains within the alternatively spliced region. These results suggest that the effect of tenascin on axon growth is a function of splice variants, as well as the form or conformation of those variants.