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Novel roles of the chemorepellent axon guidance molecule RGMa in cell migration and adhesion.

Abstract

The repulsive guidance molecule A (RGMa) is a contact-mediated axon guidance molecule that has significant roles in central nervous system (CNS) development. Here we have examined whether RGMa has novel roles in cell migration and cell adhesion outside the nervous system. RGMa was found to stimulate cell migration from Xenopus animal cap explants in a neogenin-dependent and BMP-independent manner. RGMa also stimulated the adhesion of Xenopus animal cap cells, and this adhesion was dependent on neogenin and independent of calcium. To begin to functionally characterize the role of specific domains in RGMa, we assessed the migratory and adhesive activities of deletion mutants. RGMa lacking the partial von Willebrand factor type D (vWF) domain preferentially perturbed cell adhesion, while mutants lacking the RGD motif affected cell migration. We also revealed that manipulating the levels of RGMa in vivo caused major migration defects during Xenopus gastrulation. We have revealed here novel roles of RGMa in cell migration and adhesion and demonstrated that perturbations to the homeostasis of RGMa expression can severely disrupt major morphogenetic events. These results have implications for understanding the role of RGMa in both health and disease.

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  • Authors

    Lah GJ, Key B

    Source

    Molecular and cellular biology 32:5 2012 Mar pg 968-80

    MeSH

    Animals
    Bone Morphogenetic Proteins
    Calcium
    Cell Adhesion
    Cell Movement
    Embryo, Nonmammalian
    Gastrulation
    Membrane Proteins
    Morphogenesis
    Nerve Tissue Proteins
    Neurulation
    Protein Structure, Tertiary
    Xenopus
    Xenopus Proteins

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22215618