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GATA-6 promotes cell survival by up-regulating BMP-2 expression during embryonic stem cell differentiation

GATA-6 is a zinc-finger transcription factor essential for early embryogenesis. Ablation of GATA-6 in mice impairs endoderm differentiation and causes apoptosis of epiblast cells. The endoderm defects have been attributed to the loss of HNF4, disabled-2, and GATA-4. However, the mechanisms underlyin...

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Autores principales: Rong, Li, Liu, Jie, Qi, Yanmei, Graham, Alan M., Parmacek, Michael S., Li, Shaohua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442421/
https://www.ncbi.nlm.nih.gov/pubmed/22855527
http://dx.doi.org/10.1091/mbc.E12-04-0313
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author Rong, Li
Liu, Jie
Qi, Yanmei
Graham, Alan M.
Parmacek, Michael S.
Li, Shaohua
author_facet Rong, Li
Liu, Jie
Qi, Yanmei
Graham, Alan M.
Parmacek, Michael S.
Li, Shaohua
author_sort Rong, Li
collection PubMed
description GATA-6 is a zinc-finger transcription factor essential for early embryogenesis. Ablation of GATA-6 in mice impairs endoderm differentiation and causes apoptosis of epiblast cells. The endoderm defects have been attributed to the loss of HNF4, disabled-2, and GATA-4. However, the mechanisms underlying epiblast apoptosis are unclear. In this study we used mouse embryonic stem cell–derived embryoid bodies (EBs) as a model for peri-implantation development and found that ablation of GATA-6 causes massive apoptosis during EB differentiation. Endoderm grafting experiments and ectopic basement membrane (BM) assembly suggest that both BM and non-BM factors contribute to cell survival. Furthermore, the increased cell death in mutant EBs is accompanied by reduced expression of bone morphogenetic protein 2 (BMP-2). Chromatin immunoprecipitation reveals direct binding of GATA-6 to the Bmp2 promoter. Treatment of the mutant EBs with BMP-2 markedly suppresses apoptosis, whereas stable overexpression of the BMP antagonist noggin or a dominant-negative BMP receptor in normal EBs leads to increased apoptosis. Last, activation of SMAD1/5 by phosphorylation is significantly inhibited in the absence of GATA-6, and this is reversed by exogenous BMP-2. Treatment of normal EBs with SMAD phosphorylation inhibitor increases apoptosis. Collectively these results suggest that GATA-6 promotes cell survival by regulating endoderm expression of BMP-2 and BM during embryonic epithelial morphogenesis.
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spelling pubmed-34424212012-11-30 GATA-6 promotes cell survival by up-regulating BMP-2 expression during embryonic stem cell differentiation Rong, Li Liu, Jie Qi, Yanmei Graham, Alan M. Parmacek, Michael S. Li, Shaohua Mol Biol Cell Articles GATA-6 is a zinc-finger transcription factor essential for early embryogenesis. Ablation of GATA-6 in mice impairs endoderm differentiation and causes apoptosis of epiblast cells. The endoderm defects have been attributed to the loss of HNF4, disabled-2, and GATA-4. However, the mechanisms underlying epiblast apoptosis are unclear. In this study we used mouse embryonic stem cell–derived embryoid bodies (EBs) as a model for peri-implantation development and found that ablation of GATA-6 causes massive apoptosis during EB differentiation. Endoderm grafting experiments and ectopic basement membrane (BM) assembly suggest that both BM and non-BM factors contribute to cell survival. Furthermore, the increased cell death in mutant EBs is accompanied by reduced expression of bone morphogenetic protein 2 (BMP-2). Chromatin immunoprecipitation reveals direct binding of GATA-6 to the Bmp2 promoter. Treatment of the mutant EBs with BMP-2 markedly suppresses apoptosis, whereas stable overexpression of the BMP antagonist noggin or a dominant-negative BMP receptor in normal EBs leads to increased apoptosis. Last, activation of SMAD1/5 by phosphorylation is significantly inhibited in the absence of GATA-6, and this is reversed by exogenous BMP-2. Treatment of normal EBs with SMAD phosphorylation inhibitor increases apoptosis. Collectively these results suggest that GATA-6 promotes cell survival by regulating endoderm expression of BMP-2 and BM during embryonic epithelial morphogenesis. The American Society for Cell Biology 2012-09-15 /pmc/articles/PMC3442421/ /pubmed/22855527 http://dx.doi.org/10.1091/mbc.E12-04-0313 Text en © 2012 Rong et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Rong, Li
Liu, Jie
Qi, Yanmei
Graham, Alan M.
Parmacek, Michael S.
Li, Shaohua
GATA-6 promotes cell survival by up-regulating BMP-2 expression during embryonic stem cell differentiation
title GATA-6 promotes cell survival by up-regulating BMP-2 expression during embryonic stem cell differentiation
title_full GATA-6 promotes cell survival by up-regulating BMP-2 expression during embryonic stem cell differentiation
title_fullStr GATA-6 promotes cell survival by up-regulating BMP-2 expression during embryonic stem cell differentiation
title_full_unstemmed GATA-6 promotes cell survival by up-regulating BMP-2 expression during embryonic stem cell differentiation
title_short GATA-6 promotes cell survival by up-regulating BMP-2 expression during embryonic stem cell differentiation
title_sort gata-6 promotes cell survival by up-regulating bmp-2 expression during embryonic stem cell differentiation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442421/
https://www.ncbi.nlm.nih.gov/pubmed/22855527
http://dx.doi.org/10.1091/mbc.E12-04-0313
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