The Journal of Neuroscience, January 15, 1999, 19(2):813-827
Tenascin-R Inhibits the Growth of Optic Fibers In
Vitro But Is Rapidly Eliminated during Nerve Regeneration in the
Salamander Pleurodeles waltl
Catherina G.
Becker1, 2,
Thomas
Becker1, 2,
Ronald L.
Meyer2, 3, and
Melitta
Schachner1, 3
1 Zentrum für Molekulare Neurobiologie Hamburg,
Universität Hamburg, D-20246 Hamburg, Germany, and
2 Department of Developmental and Cell Biology, University
of California, Irvine, California 92697
Tenascin-R is a multidomain molecule of the extracellular matrix in
the CNS with neurite outgrowth inhibitory functions. Despite the fact
that in amphibians spontaneous axonal regeneration of the optic nerve
occurs, we show here that the molecule appears concomitantly with
myelination during metamorphosis and is present in the adult optic
nerve of the salamander Pleurodeles waltl by immunoblots
and immunohistochemistry. In vitro, adult retinal ganglion 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 presence of laminin, indicating that tenascin-R inhibits
regrowth of retinal ganglion cell axons. After an optic nerve crush,
immunoreactivity for tenascin-R was reduced to undetectable levels
within 8 d. Immunoreactivity for the myelin-associated glycoprotein (MAG) was also diminished by that time. Myelin was removed
by phagocytosing cells at 8-14 d after the lesion, as demonstrated by
electron microscopy. Tenascin-R immunoreactivity was again detectable
at 6 months after the lesion, correlated with remyelination as
indicated 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 pia, as demonstrated by anterograde tracing.
Thus, the onset of axonal regrowth over the lesion site was correlated
with the removal of inhibitory molecules in the optic nerve, which may
be necessary for successful axonal regeneration in the CNS of amphibians.
Key words:
CNS injury; optic nerve; retinotectal system; extracellular matrix; amphibians; urodeles
Copyright © 1999 Society for Neuroscience 0270-6474/99/192813-15$05.00/0