Robust Axonal Regeneration Occurs in the Injured CAST/Ei Mouse CNS

Takao Omura, Kumiko Omura, Andrea Tedeschi, Priscilla Riva, Michio W. Painter, Leticia Rojas, Joshua Martin, Véronique Lisi, Eric A. Huebner, Alban Latremoliere, Yuqin Yin, Lee B. Barrett, Bhagat Singh, Stella Lee, Tom Crisman, Fuying Gao, Songlin Li, Kush Kapur, Daniel H. Geschwind, Kenneth S. KosikGiovanni Coppola, Zhigang He, S. Thomas Carmichael, Larry I. Benowitz, Michael Costigan, Clifford J. Woolf

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Axon regeneration in the CNS requires reactivating injured neurons' intrinsic growth state and enabling growth in an inhibitory environment. Using an inbred mouse neuronal phenotypic screen, we find that CAST/Ei mouse adult dorsal root ganglion neurons extend axons more on CNS myelin than the other eight strains tested, especially when pre-injured. Injury-primed CAST/Ei neurons also regenerate markedly in the spinal cord and optic nerve more than those from C57BL/6 mice and show greater sprouting following ischemic stroke. Heritability estimates indicate that extended growth in CAST/Ei neurons on myelin is genetically determined, and two whole-genome expression screens yield the Activin transcript Inhba as most correlated with this ability. Inhibition of Activin signaling in CAST/Ei mice diminishes their CNS regenerative capacity, whereas its activation in C57BL/6 animals boosts regeneration. This screen demonstrates that mammalian CNS regeneration can occur and reveals a molecular pathway that contributes to this ability. Omura et al. screened for neuronal growth on myelin and find CAST/Ei inbred mice are uniquely able to regenerate axons in the injured CNS through Activin signaling. Enhancing Activin signaling confers a CNS-regenerative capacity in normally non-regenerative mouse strains.

Original languageEnglish
Pages (from-to)1215-1227
Number of pages13
JournalNeuron
Volume86
Issue number5
DOIs
StatePublished - 3 Jun 2015
Externally publishedYes

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