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. Kosik; Giovanni Coppola; Zhigang He; S. Thomas Carmichael; Larry I. Benowitz; Michael Costigan; Clifford J. Woolf

doi:10.1016/j.neuron.2015.05.005

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 journal › Article › peer-review

45 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 language	English (US)
Pages (from-to)	1215-1227
Number of pages	13
Journal	Neuron
Volume	86
Issue number	5
DOIs	https://doi.org/10.1016/j.neuron.2015.05.005
State	Published - Jun 3 2015
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience

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Omura, T., Omura, K., Tedeschi, A., Riva, P., Painter, M. W., Rojas, L., Martin, J., Lisi, V., Huebner, E. A., Latremoliere, A., Yin, Y., Barrett, L. B., Singh, B., Lee, S., Crisman, T., Gao, F., Li, S., Kapur, K., Geschwind, D. H., ... Woolf, C. J. (2015). Robust Axonal Regeneration Occurs in the Injured CAST/Ei Mouse CNS. Neuron, 86(5), 1215-1227. https://doi.org/10.1016/j.neuron.2015.05.005

Omura, T, Omura, K, Tedeschi, A, Riva, P, Painter, MW, Rojas, L, Martin, J, Lisi, V, Huebner, EA, Latremoliere, A, Yin, Y, Barrett, LB, Singh, B, Lee, S, Crisman, T, Gao, F, Li, S, Kapur, K, Geschwind, DH, Kosik, KS, Coppola, G, He, Z, Carmichael, ST, Benowitz, LI, Costigan, M & Woolf, CJ 2015, 'Robust Axonal Regeneration Occurs in the Injured CAST/Ei Mouse CNS', Neuron, vol. 86, no. 5, pp. 1215-1227. https://doi.org/10.1016/j.neuron.2015.05.005

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title = "Robust Axonal Regeneration Occurs in the Injured CAST/Ei Mouse CNS",

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.",

author = "Takao Omura and Kumiko Omura and Andrea Tedeschi and Priscilla Riva and Painter, {Michio W.} and Leticia Rojas and Joshua Martin and V{\'e}ronique Lisi and Huebner, {Eric A.} and Alban Latremoliere and Yuqin Yin and Barrett, {Lee B.} and Bhagat Singh and Stella Lee and Tom Crisman and Fuying Gao and Songlin Li and Kush Kapur and Geschwind, {Daniel H.} and Kosik, {Kenneth S.} and Giovanni Coppola and Zhigang He and Carmichael, {S. Thomas} and Benowitz, {Larry I.} and Michael Costigan and Woolf, {Clifford J.}",

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doi = "10.1016/j.neuron.2015.05.005",

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T1 - Robust Axonal Regeneration Occurs in the Injured CAST/Ei Mouse CNS

AU - Omura, Takao

AU - Omura, Kumiko

AU - Tedeschi, Andrea

AU - Riva, Priscilla

AU - Painter, Michio W.

AU - Rojas, Leticia

AU - Martin, Joshua

AU - Lisi, Véronique

AU - Huebner, Eric A.

AU - Latremoliere, Alban

AU - Yin, Yuqin

AU - Barrett, Lee B.

AU - Singh, Bhagat

AU - Lee, Stella

AU - Crisman, Tom

AU - Gao, Fuying

AU - Li, Songlin

AU - Kapur, Kush

AU - Geschwind, Daniel H.

AU - Kosik, Kenneth S.

AU - Coppola, Giovanni

AU - He, Zhigang

AU - Carmichael, S. Thomas

AU - Benowitz, Larry I.

AU - Costigan, Michael

AU - Woolf, Clifford J.

PY - 2015/6/3

Y1 - 2015/6/3

N2 - 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.

AB - 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.

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JO - Neuron

JF - Neuron

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ER -

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

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