The repulsive guidance molecule, RGMa, promotes retinal ganglion cell survival in vitro and in vivo

Koeberle, Paulo D.; Tura, Aysegül; Tassew, Nardos G.; Schlichter, Lyanne C.; Monnier, Philippe P.

doi:10.1016/j.neuroscience.2010.04.079

Cited by 31 publications

(25 citation statements)

References 36 publications

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“…The neogenin pattern in our ONC, ONC + LI, SHM or SHM + LI-operated animals was unchanged compared to the pattern of untreated animals in a recent publication [30]. Koeberle et al reported a clear staining of RGC somata and a weak staining of nerve fibers.…”

Section: Discussioncontrasting

confidence: 48%

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RGMA and neogenin protein expression are influenced by lens injury following optic nerve crush in the rat retina

Schnichels

Heiduschka

Julien

2011

Graefes Arch Clin Exp Ophthalmol

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Although a difference in the localization of RGMA is not obvious, the difference in the amount of RGMA is striking, the higher amount of RGMA in the retinae of ONC + LI rats compared to ONC rats indicates a role for RGMA during degeneration/regeneration processes. Our results are consistent with several reported neuroprotective effects of RGMA. Our new data showing the upregulation of RGMA after ONC in our regenerating model (plus LI) confirm these findings conducted in different settings.

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Section: Discussioncontrasting

confidence: 48%

“…Matsunaga et al concluded a proapoptotic role for neogenin if it is not bound to its ligand RGMA [29]. Moreover, it was recently shown that RGMA promotes retinal ganglion cell survival in vivo and in vitro [30].…”

Section: Introductionmentioning

confidence: 99%

RGMA and neogenin protein expression are influenced by lens injury following optic nerve crush in the rat retina

Schnichels

Heiduschka

Julien

2011

Graefes Arch Clin Exp Ophthalmol

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“…Neogenin has been proposed to act as a dependence receptor, whereby binding of RGM to neogenin is necessary to prevent neogenin-induced cell death in the chick neural tube (Matsunaga et al, 2004). By contrast, RGMA-induced neogenin signaling promotes the survival of retinal ganglion cells in the chick retina or induces cell death in the early Xenopus embryo (Shin and Wilson, 2008;Koeberle et al, 2010). We found that ablation of neogenin expression induces robust cell death, which is consistent with a role for neogenin signaling in promoting survival rather than cell death in the mouse OE.…”

Section: Neogenin In Neuronal Survivalmentioning

confidence: 99%

“…RGMs are GPIanchored proteins widely expressed in the nervous system that can repel axons in a neogenin-dependent fashion (Conrad et al, 2010;Monnier et al, 2002;Oldekamp et al, 2004;O'Leary et al, 2013;Rajagopalan et al, 2004;Tassew et al, 2012;Wilson and Key, 2006). Furthermore, RGM-neogenin signaling has been implicated in the regulation of neuronal differentiation, neural tube closure and neuronal survival (Kee et al, 2008;Koeberle et al, 2010;Matsunaga et al, 2006Matsunaga et al, , 2004O'Leary et al, 2015;Shin and Wilson, 2008).…”

Section: Introductionmentioning

confidence: 99%

RGMB and neogenin control cell differentiation in the developing olfactory epithelium

et al. 2016

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Cellular interactions are key for the differentiation of distinct cell types within developing epithelia, yet the molecular mechanisms engaged in these interactions remain poorly understood. In the developing olfactory epithelium (OE), neural stem/progenitor cells give rise to odorant-detecting olfactory receptor neurons (ORNs) and glial-like sustentacular (SUS) cells. Here, we show in mice that the transmembrane receptor neogenin (NEO1) and its membranebound ligand RGMB control the balance of neurons and glial cells produced in the OE. In this layered epithelium, neogenin is expressed in progenitor cells, while RGMB is restricted to adjacent newly born ORNs. Ablation of Rgmb via gene-targeting increases the number of dividing progenitor cells in the OE and leads to supernumerary SUS cells. Neogenin loss-of-function phenocopies these effects observed in Rgmb −/− mice, supporting the proposal that RGMB-neogenin signaling regulates progenitor cell numbers and SUS cell production. Interestingly, Neo1−/− mice also exhibit increased apoptosis of ORNs, implicating additional ligands in the neogenin-dependent survival of ORNs. Thus, our results indicate that RGMB-neogenin-mediated cellcell interactions between newly born neurons and progenitor cells control the ratio of glia and neurons produced in the OE.

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“…[1][2][3] Thought to be exclusively expressed in the central nervous system (CNS), RGMa has been recently found to be expressed in spleen, monocytes, and lymphocytes, which suggests a role within the immune system. 4 Futhermore, a study on multiple sclerosis (MS) and a mouse model of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), in which dendritic cells (DCs) play an irreplaceable role, demonstrates that application of a RGMa-neutralizing antibody can reduce the clinical signs and immune responses of EAE by DCs.…”

Section: Introductionmentioning

confidence: 99%

Repulsive guidance molecule a blockade exerts the immunoregulatory function in DCs stimulated with ABP and LPS

Gao

Zhai

et al. 2016

Human Vaccines & Immunotherapeutics

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Repulsive guidance molecule a (RGMa) is an axonal guidance molecule that has recently found to exert function in immune system. This study evaluated the function of RGMa in modulation of dendritic cells (DCs) function stimulated with Achyranthes bidentata polysaccharide (ABP) and lipopolysaccharide (LPS) using a RGMa-neutralizing antibody. Compared with the Control-IgG/ABP and Control-IgG/LPS groups, DCs in the Anti-RGMa/ABP and Anti-RGMa/LPS groups 1) showed small, round cells with a few cell processes and organelles, and many pinocytotic vesicles; 2) had decreased MHC II, CD86, CD80, and CD40 expression; 3) displayed the decreased IL-12p70, IL-1b and TNF-a levels and increased IL-10 secretion; 4) had a high percentage of FITC-dextran uptake; and 5) displayed a reduced ability to drive T cell proliferation and reinforced T cell polarization toward a Th2 cytokine pattern. We conclude that DCs treated with RGMa-neutralizing antibodies present with tolerogenic and immunoregulatory characteristics, which provides new insights into further understanding of the function of RGMa.

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The repulsive guidance molecule, RGMa, promotes retinal ganglion cell survival in vitro and in vivo

Cited by 31 publications

References 36 publications

RGMA and neogenin protein expression are influenced by lens injury following optic nerve crush in the rat retina

RGMA and neogenin protein expression are influenced by lens injury following optic nerve crush in the rat retina

RGMB and neogenin control cell differentiation in the developing olfactory epithelium

Repulsive guidance molecule a blockade exerts the immunoregulatory function in DCs stimulated with ABP and LPS

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