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.
Links
Authors
Institution
Brain Growth and Regeneration Lab, School of Biomedical Sciences, The University of Queensland, Brisbane, Australia.
Source
Molecular and cellular biology 32:5 2012 Mar pg 968-80MeSH
AnimalsBone 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 ArticleResearch Support, Non-U.S. Gov't
Language
eng
PubMed ID
22215618
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