Inactivation of rho signaling pathway promotes CNS axon regeneration

Maxine Lehmann, Alyson Fournier, Immaculada Selles-Navarro, Pauline Dergham, Agnes Sebok, Nicole Leclerc, Gabor Tigyi, Lisa McKerracher

Research output: Contribution to journalArticle

499 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7537-7547
Number of pages11
JournalJournal of Neuroscience
Volume19
Issue number17
StatePublished - Sep 1 1999

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Axons
Regeneration
Neurites
Optic Nerve
Myelin-Associated Glycoprotein
Retinal Neurons
rho GTP-Binding Proteins
PC12 Cells
Growth
Myelin Sheath
Transfection
Enzymes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Lehmann, M., Fournier, A., Selles-Navarro, I., Dergham, P., Sebok, A., Leclerc, N., ... McKerracher, L. (1999). Inactivation of rho signaling pathway promotes CNS axon regeneration. Journal of Neuroscience, 19(17), 7537-7547.

Inactivation of rho signaling pathway promotes CNS axon regeneration. / Lehmann, Maxine; Fournier, Alyson; Selles-Navarro, Immaculada; Dergham, Pauline; Sebok, Agnes; Leclerc, Nicole; Tigyi, Gabor; McKerracher, Lisa.

In: Journal of Neuroscience, Vol. 19, No. 17, 01.09.1999, p. 7537-7547.

Research output: Contribution to journalArticle

Lehmann, M, Fournier, A, Selles-Navarro, I, Dergham, P, Sebok, A, Leclerc, N, Tigyi, G & McKerracher, L 1999, 'Inactivation of rho signaling pathway promotes CNS axon regeneration', Journal of Neuroscience, vol. 19, no. 17, pp. 7537-7547.
Lehmann M, Fournier A, Selles-Navarro I, Dergham P, Sebok A, Leclerc N et al. Inactivation of rho signaling pathway promotes CNS axon regeneration. Journal of Neuroscience. 1999 Sep 1;19(17):7537-7547.
Lehmann, Maxine ; Fournier, Alyson ; Selles-Navarro, Immaculada ; Dergham, Pauline ; Sebok, Agnes ; Leclerc, Nicole ; Tigyi, Gabor ; McKerracher, Lisa. / Inactivation of rho signaling pathway promotes CNS axon regeneration. In: Journal of Neuroscience. 1999 ; Vol. 19, No. 17. pp. 7537-7547.
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