Repulsive guidance molecule b inhibits neurite growth and is increased after spinal cord injury

Liu, Xiaoxiang; Hashimoto, Motonori; Horii, Hajime; Yamaguchi, Atsushi; Naito, Koichiro; Yamashita, Toshio

doi:10.1016/j.bbrc.2009.03.115

Cited by 26 publications

(27 citation statements)

References 15 publications

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“…Since then, RGM molecules have been associated with neural tube closure (Niederkofler et al, 2004); neuronal cell survival (Matsunaga et al, 2004); inhibition of axonal outgrowth after injury (Hata et al, 2006;Liu et al, 2009); control of neuronal proliferation and differentiation (Matsunaga et al, 2006) and inhibition of neural crest cell differentiation . Significantly, roles of RGM molecules outside the nervous system are now emerging, including reproduction (RGMb; Xia et al, 2005) and iron metabolism (RGMc; Papanikolaou et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…However, rather than facilitating axonal repulsion, RGMb was shown to promote adhesion of mouse DRG neurons (Samad et al, 2004). Further biological roles for RGMb include mammalian reproduction ; and, similar to RGMa, responses to nervous system injury (Liu et al, 2009). RGMb injection in Xenopus embryos induced endodermal, mesodermal, and in the ectoderm, neuronal markers while neural crest cell differentiation was inhibited .…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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“…Cellular motility was assessed using a cytodex-2 bead motility assay. Cells (5x10 5 ) for each cell type were incubated in 10 ml of growth medium containing 100 µl of cytodex-2 microcarrier beads (GE Healthcare, Cardiff, UK) for 3.5 h to allow the cells to adhere to the beads. After washing the beads were resuspended in growth medium, seeded into a 24-well plate and then incubated overnight at 37˚C.…”

Section: In Vitro Cell Invasion Assay Transwell Inserts (Upper Chamber)mentioning

confidence: 99%

“…RGMA mediates repulsive axonal guidance and neural tube closure, and RGMC is mutated in juvenile hemochromatosis. RGMB, also known as Dragon, is a myelin-derived inhibitor of axon growth in the central nerve system (5) and regulates the patterning of the developing nervous system (6). As BMP co-receptors, RGMA can increase binding of BMP ligands to ActRIIA, a type II receptor, and lead to an enhanced signalling by BMP-2 and BMP-4 (7).…”

Section: Introductionmentioning

confidence: 99%

Repulsive guidance molecules, novel bone morphogenetic protein co-receptors, are key regulators of the growth and aggressiveness of prostate cancer cells

Ye²,

Kynaston³

et al. 2011

Int J Oncol

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Abstract. Repulsive guidance molecule (RGM) family members RGMA, RGMB and RGMC are GPI-linked membrane proteins recently identified as co-receptor of bone morphogenetic proteins (BMPs). BMPs are a group of proteins enriched in bone and play important roles in prostate cancer. The current study aimed to investigate roles played by RGMs in prostate cancer. Expression of RGMs was examined in prostate cancer cell lines and prostate cancer tissues using RT-PCR and immunohistochemical staining. Knockdown of each RGM in prostate cancer cells was performed using the respective anti-RGMA, RGMB and RGMC transgenes. A variety of in vitro function tests were employed to analyze the influence on cancer cell functions by RGM knockdown. The implications of RGM knockdown in BMP signalling were also examined using both Western blot and real-time quantitative PCR. Knockdown of RGMA had no effect on cell growth, migration and invasion, but promoted cell-matrix adhesion. Knockdown of RGMB and RGMC increased growth and adhesion, but only RGMB knockdown increased capacities of migration and invasion in PC-3 cells. Further investigations showed an increase in Smad-3 activation and reduced levels of Smad-1 in PC-3 cells by RGMB and RGMC knockdown, and also an up-regulation of ID1, a BMP target gene particularly in exposure to BMP7. RGMs play inhibitory roles in prostate cancer by suppressing cell growth, adhesion, migration and invasion. RGMs can coordinate Smad-dependent signalling of BMPs in prostate cancer cells.

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“…RGMb has also been shown to be involved in promoting mouse dorsal root ganglion (DRG) neuron adhesion (11), has been implicated in axonal regeneration after injury (12) and in response to spinal cord injury, where it is found to be upregulated (13). In addition to its roles in the nervous system, RGMb has also been shown to contribute to bone morphogenetic protein (BMP) signalling, where it has been identified, together with RGMa and RGMc, as a BMP co-receptor (14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Tumour angiogenesis and repulsive guidance molecule b: A role in HGF- and BMP-7-mediated angiogenesis

Sanders

et al. 2014

International Journal of Oncology

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Abstract. Hepatocyte growth factor (HGF) is a key growth factor linked to promoting cancer progression and angiogenesis. The present study identifies repulsive guidance molecule b (RGMb), a bone morphogenetic protein (BMP) co-receptor, as a gene whose expression is regulated by HGF and explores the potential of RGMb to contribute to the process of angiogenesis. Microarray analysis was used to identify HGF responsive genes in HECV endothelial cells, identifying RGMb. RGMb was subsequently targeted using a ribozyme transgene system and its role in angiogenesis assessed using in vitro and in vivo assays. The importance of RGMb in pro-angiogenic responses to HGF and BMP-7 was also assessed. Microarray analysis identified RGMb as a gene upregulated as a result of HGF treatment. Knockdown of RGMb, in HECV cells, had minimal effects on tubule formation, brought about a general, although non-significant increase in cell growth and enhanced cell migration. Similarly, no significant effect of RGMb knockdown was found in vivo using a co-inoculation angiogenesis model. Knockdown of RGMb was, however, found to reduce the responsiveness of HECV cells to HGF treatment and particularly to BMP-7 treatment in regard to the enhanced migratory and tubule formation brought about by these treatments in vitro. Our results indicate that RGMb expression can be influenced by HGF treatment. Whilst this molecule appears to have minimal impact on angiogenic traits individually, it demonstrates an involvement in propagating pro-angiogenic effects of HGF and particularly BMP-7 and thus, may play a role in regulating angiogenic responses to HGF and BMP-7.

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Repulsive guidance molecule b inhibits neurite growth and is increased after spinal cord injury

Cited by 26 publications

References 15 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

Repulsive guidance molecules, novel bone morphogenetic protein co-receptors, are key regulators of the growth and aggressiveness of prostate cancer cells

Tumour angiogenesis and repulsive guidance molecule b: A role in HGF- and BMP-7-mediated angiogenesis

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