Tenascin-R inhibits the growth of optic fibers in vitro but is rapidly eliminated during nerve regeneration in the salamander Pleurodeles waltl

Tenascin-R is a multidomain molecule of the extracellular matrix in the CNS with neurite outgrowth inhibitory functions. Despite the fact that in amph ibians spontaneous axonal regeneration of the optic nerve occurs, we show h ere that the molecule appears concomitantly with myelination during metamor phosis and is present in the adult optic nerve of the salamander Pleurodele s waltI by immunoblots and immunohistochemistry. In vitro, adult retinal ga nglion cell axons were not able to grow from retinal explants on a tenascin -R substrate or to cross a sharp substrate border of tenascin-R in the pres ence of laminin, indicating that tenascin-R inhibits regrowth of retinal ga nglion cell axons. After an optic nerve crush, immunoreactivity for tenasci n-R was reduced to undetectable levels within 8 d. Immunoreactivity for the myelin-associated glycoprotein (MAG) was also diminished by that time. Mye lin was removed by phagocytosing cells at 8-14 d after the lesion, as demon strated by electron microscopy. Tenascin-R immunoreactivity was again detec table at 6 months after the lesion, correlated with remyelination as indica ted by MAG immunohistochemistry. Regenerating axons began to repopulate the distal lesioned nerve at 9 d after a crush and grew in close contact with putative astrocytic processes in the periphery of the nerve, close to the p ia, as demonstrated by anterograde tracing. Thus, the onset of axonal regro wth over the lesion site was correlated with the removal of inhibitory mole cules in the optic nerve, which may be necessary for successful axonal rege neration in the CNS of amphibians.