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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. and Brenner, Gary J. and Omura, Takao and Samad, Omar A. and Costigan, Michael and Inquimbert, Perrine and Niederkofler, Vera and Salie, Rishard and Sun, Chia C. and Lin, Herbert Y. and Arber, Silvia and Coppola, Giovanni and Woolfe, Clifford J. and Samad, T. A.. (2011) The BMP Coreceptor RGMb Promotes While the Endogenous BMP Antagonist Noggin Reduces Neurite Outgrowth and Peripheral Nerve Regeneration by Modulating BMP Signaling. Journal of Neuroscience, 31 (50). pp. 18391-18400.

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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 neurons from RGMb−/− mice exhibited significantly fewer and shorter neurites than those from wild-type littermates, a phenomenon that could be fully rescued by BMP-2. Moreover, Noggin, an endogenous BMP signaling antagonist, inhibited neurite outgrowth in wild-type DRG explants from naive as well as nerve injury-preconditioned mice. Noggin is downregulated 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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Arber)
UniBasel Contributors:Arber, Silvia
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Society for Neuroscience
ISSN:0270-6474
e-ISSN:1529-2401
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:27 Nov 2017 14:07
Deposited On:14 Sep 2012 06:38

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