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The Journal of Neuroscience, September 1, 1999, 19(17):7537-7547
Inactivation of Rho Signaling Pathway Promotes CNS Axon Regeneration
Maxine Lehmann1, Alyson Fournier1, Immaculada Selles-Navarro1, Pauline Dergham1, Agnes Sebok2, Nicole Leclerc1, Gabor Tigyi2, and Lisa McKerracher1 1 Département de Pathologie et Biologie Cellulaire, Université de Montréal, Succursale Centreville, Montréal, Québec H3C 3J7, Canada, and 2 Department of Physiology, University of Tennessee, Memphis, Tennessee 38163
Regeneration in the CNS is blocked by many different growth inhibitory proteins. To foster regeneration, we have investigated a strategy to block the neuronal response to growth inhibitory signals. Here, we report that injured axons regrow directly on complex inhibitory substrates when Rho GTPase is inactivated. Treatment of PC12 cells with C3 enzyme to inactivate Rho and transfection with dominant negative Rho allowed neurite growth on inhibitory substrates. Primary retinal neurons treated with C3 extended neurites on myelin-associated glycoprotein and myelin substrates. To explore regeneration in vivo, we crushed optic nerves of adult rat. After C3 treatment, numerous cut axons traversed the lesion to regrow in the distal white matter of the optic nerve. These results indicate that targeting signaling mechanisms converging to Rho stimulates axon regeneration on inhibitory CNS substrates.
Key words: retinal ganglion cells; optic nerve; Rho GTPase; microcrush lesion; C3 toxin; myelin-associated growth inhibitory proteins; MAG
Copyright © 1999 Society for Neuroscience 0270-6474/99/19177537-11$05.00/0
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