title: Development of the mammalian axial skeleton requires signaling through the Gα(i) subfamily of heterotrimeric G proteins.
abstract: 129/SvEv mice with a loss-of-function mutation in the heterotrimeric G protein α-subunit gene Gnai3 have fusions of ribs and lumbar vertebrae, indicating a requirement for Gα(i) (the "inhibitory" class of α-subunits) in somite derivatives. Mice with mutations of Gnai1 or Gnai2 have neither defect, but loss of both Gnai3 and one of the other two genes increases the number and severity of rib fusions without affecting the lumbar fusions. No myotome defects are observed in Gnai3/Gnai1 double-mutant embryos, and crosses with a conditional allele of Gnai2 indicate that Gα(i) is specifically required in cartilage precursors. Penetrance and expressivity of the rib fusion phenotype is altered in mice with a mixed C57BL/6 × 129/SvEv genetic background. These phenotypes reveal a previously unknown role for G protein-coupled signaling pathways in development of the axial skeleton.
authors.affiliation: Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health/Department of Health and Human Services, Durham, NC 27709, USA. plummer@niehs.nih.gov
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Plummer
authors.forename: Karsten
authors.initials: K
authors.lastname: Spicher
authors.forename: Jason
authors.initials: J
authors.lastname: Malphurs
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Joel
authors.initials: J
authors.lastname: Abramowitz
authors.forename: Bernd
authors.initials: B
authors.lastname: Nürnberg
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
mesh_terms: D000483:Alleles; D000818:Animals; D001846:Bone Development; D001842:Bone and Bones / Q000378:metabolism*; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000235:genetics / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000002:abnormalities / Q000254:growth & development; D008322:Mammals / Q000254:growth & development*; D051379:Mice; D057507:Mice, 129 Strain; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012272:Ribs / Q000002:abnormalities / Q000254:growth & development; D015398:Signal Transduction; D013123:Spinal Fusion; D013249:Sternum / Q000002:abnormalities / Q000254:growth & development
chemical_list: D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C498016:Gnai2 protein, mouse; C417708:Gnai3 protein, mouse