TENASCIN-C SYNTHESIS AND INFLUENCE ON AXONAL GROWTH DURING RAT CORTICAL DEVELOPMENT

Several putative guidance molecules are restricted to the marginal and subplate zones, the major fibre tracts in the developing cortex. It i s presently unknown how their distribution is achieved and how these m olecules affect neurite extension. Tenascin-C is of particular interes t in this context, because it may either promote or deflect growing ax ons depending on its mode of presentation. Therefore, the cellular ori gin of tenascin-C in the developing rat cortex and its effects on the extension of cortical afferents and efferents were examined. Tenascin- C protein is first restricted to the marginal and subplate zones and s preads later into the developing grey matter, in close correlation wit h afferent innervation. In situ hybridization showed that tenascin-C m RNA is first confined to the ventricular zone, at some distance from t he location of the protein, while at later stages tenascin-C-synthesiz ing cells become scattered throughout the cortical thickness, concomit ant with the spread of the protein. In order to assess its function, m onoclonal antibodies directed against different domains of tenascin-C were used in a quantitative axonal outgrowth assay. These perturbation experiments suggested that distinct tenascin-C fibronectin type III r epeats sustain the growth of thalamic and cortical axons on cortical m embrane carpets, whereas the EGF-type repeats are not involved. The co mbination of different antibodies revealed that separate fibronectin-t ype III repeats exert cooperative effects. These results suggest that ventricular zone cells regulate the establishment of thalamic and cort ical axonal projections through locally restricted deposition of tenas cin-C.