Since tenascin may influence neuronal cell development, we studied its expression pattern using immunocytochemistry, in situ hybridization, Northern blot analysis, and immunochemistry in the developing and adult mouse cerebellar cortex. Tenascin immunoreactivity was detectable in all layers of the developing cerebellar cortex. In the external granular layer, only the radially oriented processes of Golgi epithelial cells were immunoreactive, whereas the densely packed cell bodies were immunonegative. Tenascin was hardly detectable at contact sites between migrating granule cells and processes of Golgi epithelial cells. Axons of granule cells in the molecular layer were immunoreactive, whereas their cell bodies in the internal granular layer lacked detectable levels of tenascin. By in situ hybridization, only Golgi epithelial cells and astrocytes of the internal granular layer and prospective white matter, but not nerve cells, could be shown to synthesize detectable levels of tenascin mRNA in the developing mouse cerebellar cortex. Thus, tenascin in the cerebellar cortex seems to be a glia-derived molecule that becomes adsorbed to neuronal surfaces in a topographically restricted pattern in situ. Levels of tenascin protein and mRNA decreased significantly with increasing age. In the adult, tenascin immunoreactivity was weak and mainly restricted to the molecular layer and tenascin mRNA was confined to Golgi epithelial cells, indicative for a functional heterogeneity in differentiated cerebellar astrocytes. Quantitative immunoblot analysis revealed that the 225 and 240 kDa components of tenascin were developmentally downregulated at a faster rate than the 190 and 200 kDa components, corresponding to the faster downregulation of the 8 kilobase (kb) mRNA species compared to the 6 kb mRNA species as revealed by Northern blot analysis. These observations indicate a differentially regulated expression of the tenascin components. We hypothesize that glia-derived tenascin modifies the functional properties of nerve cell surfaces and that tenascin is involved in such different morphogenetic events as neurite growth and oligodendrocyte distribution.