RGMb controls aggregation and migration of Neogenin-positive cells in vitro and in vivo

Conrad, Sabine; Stimpfle, Fabian; Montazeri, Sonia; Oldekamp, Judit; Seid, Karin; Álvarez-Bolado, Gonzalo; Skutella, Thomas

doi:10.1016/j.mcn.2009.11.003

Cited by 21 publications

(23 citation statements)

References 29 publications

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“…Moreover, RGMa expression in the mes-and telencephalon is the same for chicken, mouse, Xenopus, and zebrafish (Matsunaga et al, 2004;Schmidtmer and Engelkamp, 2004;Samad et al, 2004;Oldekamp et al, 2004;Wilson and Key, 2006;Gessert et al, 2008;Kee et al, 2008). Likewise, RGMb expression in the mantle layer of the neural tube is known for mouse RGMb, and RGMb expression in the trigeminal ganglion, DRG, and optic stalk has been described for mouse and zebrafish (Samad et al, 2004Conrad et al, 2010). This suggests that RGMa and RGMb have conserved roles in the development of the nervous system in all gnathostome vertebrates.…”

Section: Developmental Dynamicsmentioning

confidence: 87%

RGMa and RGMb expression pattern during chicken development suggest unexpected roles for these repulsive guidance molecules in notochord formation, somitogenesis, and myogenesis

Jorge

Ahmed

Bothe

et al. 2012

Developmental Dynamics

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Background: Repulsive guidance molecules (RGM) are high-affinity ligands for the Netrin receptor Neogenin, and they are crucial for nervous system development including neural tube closure; neuronal and neural crest cell differentiation and axon guidance. Recent studies implicated RGM molecules in bone morphogenetic protein signaling, which regulates a variety of developmental processes. Moreover, a role for RGMc in iron metabolism has been established. This suggests that RGM molecules may play important roles in non-neural tissues. Results: To explore which tissues and processed may be regulated by RGM molecules, we systematically investigated the expression of RGMa and RGMb, the only RGM molecules currently known for avians, in the chicken embryo. Conclusions: Our study suggests so far unknown roles of RGM molecules in notochord, somite and skeletal muscle development. Developmental Dynamics 241: [1886][1887][1888][1889][1890][1891][1892][1893][1894][1895][1896][1897][1898][1899][1900] 2012. V C 2012 Wiley Periodicals, Inc.Key words: RGMa; DRAGON; RGMb; chicken; embryo; neural plate, neurogenesis; dorsal root ganglia; pharyngeal ectoderm; notochord; somite; dermomyotome; myotome Key findings:RGMa and RGMb expression patterns in neural tissues are conserved in gnathostome vertebrates. RGMa might be associated with muscle stem cells capable of undertaking myogenesis, and RGMb with cells ready to enter myogenic differentiation. Developmental DynamicsABBREVIATIONS asp anterior segmental plate di diencephalon dm dermomyotome dml dorsomedial lip of the dermomyotome drg dorsal root ganglion ect ectoderm edl Extensor Digitorum Longus end endoderm f fibula bone fge foregut endoderm fp floor plate of the neural tube hm head mesoderm hy hyoid (2nd) pharyngeal arch m myotome ma mandibular (1st) pharyngeal arch mes mesencephalon mx maxillary aspect of the 1st pharyngeal arch myel myelencephalon node Hensen's node (avian organizer) not notochord np neural plate nt neural tube op otic placode os optic stalk ov otic vesicle pa pharyngeal arch pchpl prechordal plate p/not posterior notochord ps primitive streak r1 r2 etc rhombomere 1 rhombomere 2 etc. s0 epithelializing somite s1 s5 etc 1st somite 5th somite etc. t tibiotarsal bone tel telencephalon V trigeminal (5th cranial nerve) ganglion VII facial (7th cranial nerve) ganglion vll ventromedial lip of the dermomyotome.Additional Supporting information may be found in the online version of this article.

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Section: Developmental Dynamicsmentioning

confidence: 87%

RGMa and RGMb expression pattern during chicken development suggest unexpected roles for these repulsive guidance molecules in notochord formation, somitogenesis, and myogenesis

Jorge

Ahmed

Bothe

et al. 2012

Developmental Dynamics

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“…While the role of RGMc (also known as hemojuvelin) in regulating iron homeostasis is well established (Babitt et al, 2006; Niederkofler et al, 2005), less is known about the roles of RGMa and RGMb in the nervous system. RGMa is suggested to contribute to neuronal differentiation and axonal guidance (Matsunaga et al, 2006; Liu et al, 2009; Severyn et al, 2009; Conrad et al, 2010) however, RGMa deficient mice do not display alterations in neuronal patterning and retinal projection topography (Niederkofler et al, 2004). …”

Section: Introductionmentioning

confidence: 99%

The BMP Coreceptor RGMb Promotes While the Endogenous BMP Antagonist Noggin Reduces Neurite Outgrowth and Peripheral Nerve Regeneration by Modulating BMP Signaling

Eddie¹,

Brenner²,

Ômura³

et al. 2011

J. Neurosci.

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Repulsive guidance molecule b (RGMb) is a bone morphogenetic protein (BMP) co-receptor and sensitizer of BMP signaling, highly expressed in adult dorsal root ganglion (DRG) sensory neurons. We used a murine RGMb knockout to gain insight into the physiological role of RGMb in the DRG, and address if RGMb-mediated modulation of BMP signaling influences sensory axon regeneration. No evidence for altered development of the peripheral and central nervous systems 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 wildtype 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 naïve 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 re-growth after nerve injury in vivo and a negative effect of Noggin.

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“…In particular, neogenin binds to HJV, like other RGM family members (Matsunaga et al, 2004; Zhang et al, 2005; Conrad et al, 2010). Moreover, neogenin mutant mice exhibit reduced hepcidin levels and iron overload consistent with a role for neogenin in regulating hepcidin and systemic iron balance in vivo (Lee et al, 2010).…”

Section: Interaction Of Hjv and The Bmp-smad Signaling Pathway With Omentioning

confidence: 99%

Hemojuvelin and bone morphogenetic protein (BMP) signaling in iron homeostasis

2014

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Mutations in hemojuvelin (HJV) are the most common cause of the juvenile-onset form of the iron overload disorder hereditary hemochromatosis. The discovery that HJV functions as a co-receptor for the bone morphogenetic protein (BMP) family of signaling molecules helped to identify this signaling pathway as a central regulator of the key iron hormone hepcidin in the control of systemic iron homeostasis. This review highlights recent work uncovering the mechanism of action of HJV and the BMP-SMAD signaling pathway in regulating hepcidin expression in the liver, as well as additional studies investigating possible extra-hepatic functions of HJV. This review also explores the interaction between HJV, the BMP-SMAD signaling pathway and other regulators of hepcidin expression in systemic iron balance.

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RGMb controls aggregation and migration of Neogenin-positive cells in vitro and in vivo

Cited by 21 publications

References 29 publications

RGMa and RGMb expression pattern during chicken development suggest unexpected roles for these repulsive guidance molecules in notochord formation, somitogenesis, and myogenesis

RGMa and RGMb expression pattern during chicken development suggest unexpected roles for these repulsive guidance molecules in notochord formation, somitogenesis, and myogenesis

The BMP Coreceptor RGMb Promotes While the Endogenous BMP Antagonist Noggin Reduces Neurite Outgrowth and Peripheral Nerve Regeneration by Modulating BMP Signaling

Hemojuvelin and bone morphogenetic protein (BMP) signaling in iron homeostasis

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