title: Ric-8A, a guanine nucleotide exchange factor for heterotrimeric G proteins, is critical for cranial neural crest cell migration.
abstract: The neural crest (NC) is a transient embryonic structure induced at the border of the neural plate. NC cells extensively migrate towards diverse regions of the embryo, where they differentiate into various derivatives, including most of the craniofacial skeleton and the peripheral nervous system. The Ric-8A protein acts as a guanine nucleotide exchange factor for several Gα subunits, and thus behaves as an activator of signaling pathways mediated by heterotrimeric G proteins. Using in vivo transplantation assays, we demonstrate that Ric-8A levels are critical for the migration of cranial NC cells and their subsequent differentiation into craniofacial cartilage during Xenopus development. NC cells explanted from Ric-8A morphant embryos are unable to migrate directionally towards a source of the Sdf1 peptide, a potent chemoattractant for NC cells. Consistently, Ric-8A knock-down showed anomalous radial migratory behavior, displaying a strong reduction in cell spreading and focal adhesion formation. We further show that during in vivo and in vitro neural crest migration, Ric-8A localizes to the cell membrane, in agreement with its role as a G protein activator. We propose that Ric-8A plays essential roles during the migration of cranial NC cells, possibly by regulating cell adhesion and spreading.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, University of Concepcion, Chile.
authors.forename: Jaime
authors.initials: J
authors.lastname: Fuentealba
authors.forename: Gabriela
authors.initials: G
authors.lastname: Toro-Tapia
authors.forename: Cecilia
authors.initials: C
authors.lastname: Arriagada
authors.forename: Lester
authors.initials: L
authors.lastname: Riquelme
authors.forename: Andrea
authors.initials: A
authors.lastname: Beyer
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Henriquez
authors.forename: Teresa
authors.initials: T
authors.lastname: Caprile
authors.forename: Roberto
authors.initials: R
authors.lastname: Mayor
authors.forename: Sylvain
authors.initials: S
authors.lastname: Marcellini
authors.forename: Maria V
authors.initials: MV
authors.lastname: Hinrichs
authors.forename: Juan
authors.initials: J
authors.lastname: Olate
authors.forename: Marcela
authors.initials: M
authors.lastname: Torrejón
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D018613:Microscopy, Confocal; D009432:Neural Crest / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D012886:Skull / Q000196:embryology / Q000294:innervation; D059008:Time-Lapse Imaging / Q000379:methods; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C525833:Ric-8 protein, Xenopus; D029867:Xenopus Proteins; D020962:Heterotrimeric GTP-Binding Proteins