The BMP coreceptor RGMb promotes while the endogenous BMP antagonist noggin reduces neurite outgrowth and peripheral nerve regeneration by modulating BMP signaling

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Gary J. Brenner
  • Takao Omura
  • Omar A. Samad
  • Michael Costigan
  • Perrine Inquimbert
  • Vera Niederkofler
  • Rishard Salie
  • Chia Chi Sun
  • Herbert Y. Lin
  • Silvia Arber
  • Giovanni Coppola
  • Clifford J. Woolf
  • Tarek A. Samad

Detail(s)

Original languageEnglish
Pages (from-to)18391-18400
Journal / PublicationJournal of Neuroscience
Volume31
Issue number50
Publication statusPublished - 14 Dec 2011

Abstract

Repulsive guidance molecule b(RGMb)is a bone morphogenetic protein(BMP)coreceptor and sensitizer of BMP signaling, highly expressed in adult dorsal root ganglion(DRG)sensory neurons. We used a murine RGMb knock-out to gain insight into the physiological role of RGMb in the DRG, and address whether RGMb-mediated modulation of BMP signaling influences sensory axon regeneration. No evidence for altered development of the PNS and CNS was detected in RGMb -/- mice. However, both cultured neonatal whole DRG explants and dissociated DRG neuronsfromRGMb -/-miceexhibitedsignificantlyfewerandshorterneuritesthanthosefromwild-typelittermates, a phenomenon that could be fully rescued by BMP-2. Moreover, Noggin, an endogenous BMP signaling antagonist, inhibited neurite out growth in wild-type DRG explants from naive as well as nerve injury-preconditioned mice. Noggin is down regulated in the DRG after nerve injury, and its expression is highly correlated and inversely associated with the known regeneration-associated genes, which are induced in the DRG by peripheral axonal injury. We show that diminished BMP signaling in vivo, achieved either through RGMb deletion or BMP inhibition with Noggin, retarded early axonal regeneration after sciatic nerve crush injury. Our data suggest a positive modulatory contribution of RGMb and BMP signaling to neurite extension in vitro and early axonal regrowth after nerve injury in vivo and a negative effect of Noggin. © 2011 the authors.

Citation Format(s)

The BMP coreceptor RGMb promotes while the endogenous BMP antagonist noggin reduces neurite outgrowth and peripheral nerve regeneration by modulating BMP signaling. / Ma, Chi H.E.; Brenner, Gary J.; Omura, Takao; Samad, Omar A.; Costigan, Michael; Inquimbert, Perrine; Niederkofler, Vera; Salie, Rishard; Sun, Chia Chi; Lin, Herbert Y.; Arber, Silvia; Coppola, Giovanni; Woolf, Clifford J.; Samad, Tarek A.

In: Journal of Neuroscience, Vol. 31, No. 50, 14.12.2011, p. 18391-18400.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal