Tgif1 and Tgif2 regulate Nodal signaling and are required for gastrulation. Development 2010 Jan;137(2):249-59
Date
12/31/2009Pubmed ID
20040491Pubmed Central ID
PMC2799159DOI
10.1242/dev.040782Scopus ID
2-s2.0-73649117155 (requires institutional sign-in at Scopus site) 57 CitationsAbstract
Tgif1 and Tgif2 are transcriptional co-repressors that limit the response to TGFbeta signaling and play a role in regulating retinoic-acid-mediated gene expression. Mutations in human TGIF1 are associated with holoprosencephaly, but it is unclear whether this is a result of deregulation of TGFbeta/Nodal signaling, or of effects on other pathways. Surprisingly, mutation of Tgif1 in mice results in only relatively mild developmental phenotypes in most strain backgrounds. Here, we show that loss-of-function mutations in both Tgif1 and Tgif2 result in a failure of gastrulation. By conditionally deleting Tgif1 in the epiblast, we demonstrate that a single wild-type allele of Tgif1 in the extra-embryonic tissue allows the double null embryos to gastrulate and begin organogenesis, suggesting that extra-embryonic Tgif function is required for patterning the epiblast. Genetically reducing the dose of Nodal in embryos lacking all Tgif function results in partial rescue of the gastrulation defects. Conditional double null embryos have defects in left-right asymmetry, which are also alleviated by reducing the dose of Nodal. Together, these data show that Tgif function is required for gastrulation, and provide the first clear evidence that Tgifs limit the transcriptional response to Nodal signaling during early embryogenesis.
Author List
Powers SE, Taniguchi K, Yen W, Melhuish TA, Shen J, Walsh CA, Sutherland AE, 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
AnimalsCell Line, Tumor
Embryo, Mammalian
Gastrulation
Gene Expression Regulation, Developmental
Homeodomain Proteins
Humans
In Situ Hybridization
Mice
Mice, Mutant Strains
Signal Transduction
