title: Tgif1 and Tgif2 Regulate Axial Patterning in Mouse.
abstract: Tgif1 and Tgif2 are transcriptional repressors that inhibit the transcriptional response to transforming growth factor β signaling, and can repress gene expression by direct binding to DNA. Loss of function mutations in TGIF1 are associated with holoprosencephaly (HPE) in humans. In mice, embryos lacking both Tgif1 and Tgif2 fail to complete gastrulation, and conditional double null embryos that survive past gastrulation have HPE and do not survive past mid-gestation. Here we show that in mice of a relatively pure C57BL/6 strain background, loss of Tgif1 alone results in defective axial patterning and altered expression of Hoxc6. The primary defects in Tgif1 null embryos are the presence of extra ribs on the C7 vertebra, consistent with a posterior transformation phenotype. In addition we observed defective cervical vertebrae, primarily C1-C5, in both adult mice and embryos that lacked Tgif1. The combination of Tgif1 and Tgif2 mutations increases the severity and penetrance of the posterior transformation phenotype, without altering the type of defects seen. Similarly, exposure of Tgif1 mutant embryos to retinoic acid at E8.5 increased the severity and penetrance of the Tgif1 phenotype. This suggests that Tgif1 and Tgif2 regulate axial patterning and that reduced TGIF function sensitizes embryos to the effects of retinoic acid.
authors.affiliation: Department of Biochemistry and Molecular Genetics, and Center for Cell Signaling, University of Virginia, Charlottesville, United States of America.
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Melhuish
authors.affiliation: Department of Biochemistry and Molecular Genetics, and Center for Cell Signaling, University of Virginia, Charlottesville, United States of America.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Taniguchi
authors.affiliation: Department of Biochemistry and Molecular Genetics, and Center for Cell Signaling, University of Virginia, Charlottesville, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Wotton
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002574:Cervical Vertebrae / Q000002:abnormalities / Q000196:embryology; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D012272:Ribs / Q000002:abnormalities / Q000196:embryology; D012863:Skeleton / Q000002:abnormalities; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D018398:Homeodomain Proteins; C080041:Hoxc6 protein, mouse; D012097:Repressor Proteins; C505201:TG-interacting factor 2, mouse; C490797:Tgif1 protein, mouse; D014212:Tretinoin