Knockout mice reveal a contribution of the extracellular matrix molecule tenascin-C to neural precursor proliferation and migration

The extracellular matrix glycoprotein tenascin-C is widely expressed in the vertebrate central nervous system (CNS) during development and repair. Des pite multiple effects of tenascin-C on cell behaviour in culture, no struct ural abnormalities of the CNS and other organs have been found in adult ten ascin-C-null mice, raising the question of whether this glycoprotein has a significant role in vivo. Using a transgenic approach, we have demonstrated that tenascin-C regulates both cell proliferation and migration tenascin-C regulates both cell proliferation and migration in oligodendrocyte precurs ors during development. Knockout mice show increased rates of oligodendrocy te precursor migration along the optic nerve and reduced rates of oligodend rocyte precursor proliferation in different regions of the CNS. Levels of p rogrammed cell death were reduced in areas of myelination at later developm ental stages, providing a potential corrective mechanism for any reduction in cell numbers that resulted from the proliferation phenotype. The effects on cell proliferation are mediated via the alphav beta3 integrin and an in teraction with the platelet-derived growth factor-stimulated mitogenic path way, emphasising the importance of both CNS extracellular matrix and integr in growth factor interactions in the regulation of neural precursor behavio ur.