Disruption of the murine homeobox gene Cdx1 affects axial skeletal identities by altering the mesodermal expression domains of Hox genes.
Cdx1 is expressed along the embryonic axis from day 7.5 postcoitum until day 12, by which time the anterior limit of expression has regressed from the hindbrain level to the forelimb bud region. To assign a functional role for Cdx1 in murine embryonic development, we have inactivated the gene via homologous recombination. Viable fertile homozygous mutant mice were obtained that show anterior homeotic transformations of vertebrae. These abnormalities were concomitant with posterior shifts of Hox gene expression domains in the somitic mesoderm. The presence of putative Cdx1-binding sites in Hox gene control regions as well as in vitro transactivation of Hoxa-7 indicates a direct regulation.
Subramanian
V
V
Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Federal Republic of Germany.
Meyer
B I
BI
Gruss
P
P
D000818:Animals; D000831:Animals, Newborn; D030161:Avian Proteins; D001483:Base Sequence; D001842:Bone and Bones / Q000196:embryology*; D002574:Cervical Vertebrae / Q000196:embryology; D004268:DNA-Binding Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005801:Genes, Homeobox / Q000502:physiology*; D018398:Homeodomain Proteins; D008159:Lumbar Vertebrae / Q000196:embryology; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D012886:Skull / Q000196:embryology; D013623:Tail / Q000196:embryology; D013904:Thoracic Vertebrae / Q000196:embryology
D030161:Avian Proteins; C491272:Cdx1 protein, mouse; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins