Tgif1 and Tgif2 Regulate Axial Patterning in Mouse. PLoS One 2016;11(5):e0155837
Date
05/18/2016Pubmed ID
27187787Pubmed Central ID
PMC4871493DOI
10.1371/journal.pone.0155837Scopus ID
2-s2.0-84969799232 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
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.
Author List
Melhuish TA, Taniguchi K, Wotton DAuthor
Kenichiro Taniguchi PhD Associate Professor in the Cell Biology Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBody Patterning
Cervical Vertebrae
Homeodomain Proteins
Mice
Mice, Inbred C57BL
Mutation
Repressor Proteins
Ribs
Skeleton
Tretinoin
