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

Abstract

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.

Spatiotemporal Expression of Repulsive Guidance Molecules (RGMs) and Their Receptor Neogenin in the Mouse Brain

“…Previous work has shown expression of RGMs and Neogenin in the proliferative zones of different brain structures [11], [18], [28], [50], [51], [67], [72], [89]. Our data confirm and extend these findings and reveal expression of Neogenin, RGMs and Unc5s in the progenitor regions of the olfactory epithelium, olfactory bulb, cortex, hippocampus and cerebellum.…”

Repulsive Guidance Molecules a, b and c Are Skeletal Muscle Proteins, and Repulsive Guidance Molecule a Promotes Cellular Hypertrophy and Is Necessary for Myotube Fusion

“…In chicken, RGMa transcripts were found in domains of epithe- lial somites that generate skeletal muscle pioneer and stem cells, and later RGM a transcripts were found at the myotome in mature somites. RGMb transcripts were found at sites of differentiated muscle cells and, at later stages, at craniofacial, limb and body muscles [Jorge et al, 2012]. In the present study, we provided new insights into the association of RGMs and skeletal muscle cells.…”

“…Recently, additional roles for RGMa and RGMb in other tissues, including skeletal muscle, have been proposed [Kanomata et al, 2009;Jorge et al, 2012]. In chicken, RGMa transcripts were found in domains of epithe- lial somites that generate skeletal muscle pioneer and stem cells, and later RGM a transcripts were found at the myotome in mature somites.…”

“…RGMc overexpression in C2C12 cells promoted myoblast differentiation and recruitment into myotubes Bae et al, 2009]. Additionally, RGMa and RGMb were both detected outside the nervous system, particularly at the somites of chicken embryos [Jorge et al, 2012]. RGMa transcripts were found in domains known to be the origin site of skeletal muscle pioneer and stem cells and, later, RGMa was found at the myotome.…”

“…RGMa transcripts were found in domains known to be the origin site of skeletal muscle pioneer and stem cells and, later, RGMa was found at the myotome. RGMb was found to overlap at sites of differentiated muscle cells and, at later stages, at craniofacial, limb and body muscles [Jorge et al, 2012]. Possible phenotypes of RGMa and RGMb in skeletal muscle cells have not been investigated thus far.…”