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.
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Takao
authors.initials: T
authors.lastname: Omura
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Omura
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tedeschi
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Riva
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Michio W
authors.initials: MW
authors.lastname: Painter
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Leticia
authors.initials: L
authors.lastname: Rojas
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Martin
authors.affiliation: Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
authors.forename: Véronique
authors.initials: V
authors.lastname: Lisi
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Huebner
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Alban
authors.initials: A
authors.lastname: Latremoliere
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Yin
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lee B
authors.initials: LB
authors.lastname: Barrett
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Bhagat
authors.initials: B
authors.lastname: Singh
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Stella
authors.initials: S
authors.lastname: Lee
authors.affiliation: Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Crisman
authors.affiliation: Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Fuying
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Neurology, David Geffen School of Medicine, and Multiple Myeloma Research Consortium, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Songlin
authors.initials: S
authors.lastname: Li
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Kush
authors.initials: K
authors.lastname: Kapur
authors.affiliation: Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.affiliation: Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kosik
authors.affiliation: Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Neurology, David Geffen School of Medicine, and Multiple Myeloma Research Consortium, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: S Thomas
authors.initials: ST
authors.lastname: Carmichael
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Larry I
authors.initials: LI
authors.lastname: Benowitz
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Anaesthesia Department, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: michael.costigan@childrens.harvard.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Costigan
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: clifford.woolf@childrens.harvard.edu.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Woolf
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D005727:Ganglia, Spinal / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D009416:Nerve Regeneration / Q000502:physiology*; D020426:Sciatic Neuropathy / Q000473:pathology / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*