Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3

Abstract Transcription factor GATA4 regulates cardiac and osteoblast differentiation. However, its role in tooth development is not clear. Therefore, we generated Wnt1-Cre;GATA4 fl/fl mice, with conditional inactivation of the GATA4 gene in the dental papilla mesenchymal cells. Phenotypic analysis s...

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Autores principales: Shuyu Guo, Yuxin Zhang, Tingting Zhou, Dongyue Wang, Yajuan Weng, Lin Wang, Junqing Ma
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:69b5792839b44590a9b8dbb15cae68192021-12-02T15:05:43ZRole of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI310.1038/s41598-017-01689-12045-2322https://doaj.org/article/69b5792839b44590a9b8dbb15cae68192017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01689-1https://doaj.org/toc/2045-2322Abstract Transcription factor GATA4 regulates cardiac and osteoblast differentiation. However, its role in tooth development is not clear. Therefore, we generated Wnt1-Cre;GATA4 fl/fl mice, with conditional inactivation of the GATA4 gene in the dental papilla mesenchymal cells. Phenotypic analysis showed short root deformity along with reduced expressions of odonto/osteogenic markers. Proliferation (but not apoptosis) of cells around the apical area of the root was attenuated. In vitro, we knocked down GATA4 expression in stem cells of dental apical papilla (SCAPs). Proliferation, migration and odonto/osteogenic differentiation of SCAPs were affected in the shGATA4 group. Overexpression of GATA4 in SCAPs increased mineralization. Based on our previous iTRAQ results, guanine nucleotide binding proteins 3 (GNAI3) is one of the distinct proteins after GATA4 deletion. G protein signaling is involved in bone development, remodeling, and disease. In this study, both GATA4 deletion in the mouse root and knock-down in human SCAPs decreased the expression of GNAI3. Dual-luciferase and ChIP assay confirmed the direct binding of GATA4 to the GNAI3 promoter, both in vitro and in vivo. GNAI3 knock-down significantly decreased the odonto/osteogenic differentiation ability of SCAPs. We thus establish the role of GATA4 as a novel regulator of root development and elucidate its downstream molecular events.Shuyu GuoYuxin ZhangTingting ZhouDongyue WangYajuan WengLin WangJunqing MaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Shuyu Guo
Yuxin Zhang
Tingting Zhou
Dongyue Wang
Yajuan Weng
Lin Wang
Junqing Ma
Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3
description Abstract Transcription factor GATA4 regulates cardiac and osteoblast differentiation. However, its role in tooth development is not clear. Therefore, we generated Wnt1-Cre;GATA4 fl/fl mice, with conditional inactivation of the GATA4 gene in the dental papilla mesenchymal cells. Phenotypic analysis showed short root deformity along with reduced expressions of odonto/osteogenic markers. Proliferation (but not apoptosis) of cells around the apical area of the root was attenuated. In vitro, we knocked down GATA4 expression in stem cells of dental apical papilla (SCAPs). Proliferation, migration and odonto/osteogenic differentiation of SCAPs were affected in the shGATA4 group. Overexpression of GATA4 in SCAPs increased mineralization. Based on our previous iTRAQ results, guanine nucleotide binding proteins 3 (GNAI3) is one of the distinct proteins after GATA4 deletion. G protein signaling is involved in bone development, remodeling, and disease. In this study, both GATA4 deletion in the mouse root and knock-down in human SCAPs decreased the expression of GNAI3. Dual-luciferase and ChIP assay confirmed the direct binding of GATA4 to the GNAI3 promoter, both in vitro and in vivo. GNAI3 knock-down significantly decreased the odonto/osteogenic differentiation ability of SCAPs. We thus establish the role of GATA4 as a novel regulator of root development and elucidate its downstream molecular events.
format article
author Shuyu Guo
Yuxin Zhang
Tingting Zhou
Dongyue Wang
Yajuan Weng
Lin Wang
Junqing Ma
author_facet Shuyu Guo
Yuxin Zhang
Tingting Zhou
Dongyue Wang
Yajuan Weng
Lin Wang
Junqing Ma
author_sort Shuyu Guo
title Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3
title_short Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3
title_full Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3
title_fullStr Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3
title_full_unstemmed Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3
title_sort role of gata binding protein 4 (gata4) in the regulation of tooth development via gnai3
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/69b5792839b44590a9b8dbb15cae6819
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