title: Repulsive guidance molecule (RGM) gene function is required for neural tube closure but not retinal topography in the mouse visual system.
abstract: The establishment of topographic projections in the developing visual system depends on the spatially and temporally controlled expression of axon guidance molecules. In the developing chick tectum, the graded expression of the repulsive guidance molecule (RGM) has been proposed to be involved in controlling the topography of the retinal ganglion cell (RGC) axon termination zones along the anteroposterior axis of the tectum. We now show that there are three mouse proteins homologous to chick RGM displaying similar proteolytic processing but exhibiting differential cell-surface targeting by glycosyl phosphatidylinositol anchor addition. Two members of this gene family (mRGMa and mRGMb) are expressed in complementary patterns in the nervous system, and mRGMa is expressed prominently in the superior colliculus at the time of anteroposterior targeting of RGC axons. The third member of the family (mRGMc) is expressed almost exclusively in skeletal muscles. Functional studies in the mouse reveal a role for mRGMa in controlling cephalic neural tube closure, thus defining an unexpected role for mRGMa in early embryonic development. In contrast, mRGMa mutant mice did not exhibit defects in anteroposterior targeting of RGC axons to their stereotypic termination zones in the superior colliculus.
authors.affiliation: Biozentrum, Department of Cell Biology, University of Basel, 4056 Basel, Switzerland
authors.forename: Vera
authors.initials: V
authors.lastname: Niederkofler
authors.forename: Rishard
authors.initials: R
authors.lastname: Salie
authors.forename: Markus
authors.initials: M
authors.lastname: Sigrist
authors.forename: Silvia
authors.initials: S
authors.lastname: Arber
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism / Q000502:physiology; D001973:Bromodeoxyuridine; D019556:COS Cells; D015816:Cell Adhesion Molecules, Neuronal; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism*; D002642:Chick Embryo; D003001:Cloning, Molecular; D036386:Ephrin-A5 / Q000235:genetics; D058851:GPI-Linked Proteins; D018507:Gene Expression Regulation, Developmental; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009928:Organ Specificity; D012160:Retina / Q000196:embryology / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013477:Superior Colliculi / Q000196:embryology / Q000378:metabolism; D000071020:Hemochromatosis Protein
chemical_list: D001973:Bromodeoxyuridine; D015816:Cell Adhesion Molecules, Neuronal; D036386:Ephrin-A5; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C483496:Rgma protein, mouse; C483497:Rgmb protein, mouse; C504414:HJV protein, mouse; D000071020:Hemochromatosis Protein