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Tgif1 and Tgif2 Regulate Axial Patterning in Mouse

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 la...

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Autores principales: Melhuish, Tiffany A., Taniguchi, Kenichiro, Wotton, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871493/
https://www.ncbi.nlm.nih.gov/pubmed/27187787
http://dx.doi.org/10.1371/journal.pone.0155837
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author Melhuish, Tiffany A.
Taniguchi, Kenichiro
Wotton, David
author_facet Melhuish, Tiffany A.
Taniguchi, Kenichiro
Wotton, David
author_sort Melhuish, Tiffany A.
collection PubMed
description 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.
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spelling pubmed-48714932016-05-31 Tgif1 and Tgif2 Regulate Axial Patterning in Mouse Melhuish, Tiffany A. Taniguchi, Kenichiro Wotton, David PLoS One Research Article 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. Public Library of Science 2016-05-17 /pmc/articles/PMC4871493/ /pubmed/27187787 http://dx.doi.org/10.1371/journal.pone.0155837 Text en © 2016 Melhuish et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Melhuish, Tiffany A.
Taniguchi, Kenichiro
Wotton, David
Tgif1 and Tgif2 Regulate Axial Patterning in Mouse
title Tgif1 and Tgif2 Regulate Axial Patterning in Mouse
title_full Tgif1 and Tgif2 Regulate Axial Patterning in Mouse
title_fullStr Tgif1 and Tgif2 Regulate Axial Patterning in Mouse
title_full_unstemmed Tgif1 and Tgif2 Regulate Axial Patterning in Mouse
title_short Tgif1 and Tgif2 Regulate Axial Patterning in Mouse
title_sort tgif1 and tgif2 regulate axial patterning in mouse
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871493/
https://www.ncbi.nlm.nih.gov/pubmed/27187787
http://dx.doi.org/10.1371/journal.pone.0155837
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