Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development

Abstract Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) has been shown to inhibit myogenesis and skeletal muscle metabolism in vitro. However, its precise role and in vivo function in muscle development has yet to be clearly defined. COUP-TFII protein expression level is hig...

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Autores principales:	Hui-Ju Lee, Chung-Yang Kao, Shih-Chieh Lin, Mafei Xu, Xin Xie, Sophia Y. Tsai, Ming-Jer Tsai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f050c0d5eaa94eabad39bd6d6f06c5fd
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spelling	oai:doaj.org-article:f050c0d5eaa94eabad39bd6d6f06c5fd2021-12-02T16:08:22ZDysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development10.1038/s41598-017-03475-52045-2322https://doaj.org/article/f050c0d5eaa94eabad39bd6d6f06c5fd2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03475-5https://doaj.org/toc/2045-2322Abstract Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) has been shown to inhibit myogenesis and skeletal muscle metabolism in vitro. However, its precise role and in vivo function in muscle development has yet to be clearly defined. COUP-TFII protein expression level is high in undifferentiated progenitors and gradually declines during differentiation, raising an important question of whether downregulation of COUP-TFII expression is required for proper muscle cell differentiation. In this study, we generated a mouse model ectopically expressing COUP-TFII in myogenic precursors to maintain COUP-TFII activity during myogenesis and found that elevated COUP-TFII activity resulted in inefficient skeletal muscle development. Using in vitro cell culture and in vivo mouse models, we showed that COUP-TFII hinders myogenic development by repressing myoblast fusion. Mechanistically, the inefficient muscle cell fusion correlates well with the transcriptional repression of Npnt, Itgb1D and Cav3, genes important for cell-cell fusion. We further demonstrated that COUP-TFII also reduces the activation of focal adhesion kinase (FAK), an integrin downstream regulator which is essential for fusion process. Collectively, our studies highlight the importance of down-regulation of COUP-TFII signaling to allow for the induction of factors crucial for myoblast fusion.Hui-Ju LeeChung-Yang KaoShih-Chieh LinMafei XuXin XieSophia Y. TsaiMing-Jer TsaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hui-Ju Lee Chung-Yang Kao Shih-Chieh Lin Mafei Xu Xin Xie Sophia Y. Tsai Ming-Jer Tsai Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development
description	Abstract Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) has been shown to inhibit myogenesis and skeletal muscle metabolism in vitro. However, its precise role and in vivo function in muscle development has yet to be clearly defined. COUP-TFII protein expression level is high in undifferentiated progenitors and gradually declines during differentiation, raising an important question of whether downregulation of COUP-TFII expression is required for proper muscle cell differentiation. In this study, we generated a mouse model ectopically expressing COUP-TFII in myogenic precursors to maintain COUP-TFII activity during myogenesis and found that elevated COUP-TFII activity resulted in inefficient skeletal muscle development. Using in vitro cell culture and in vivo mouse models, we showed that COUP-TFII hinders myogenic development by repressing myoblast fusion. Mechanistically, the inefficient muscle cell fusion correlates well with the transcriptional repression of Npnt, Itgb1D and Cav3, genes important for cell-cell fusion. We further demonstrated that COUP-TFII also reduces the activation of focal adhesion kinase (FAK), an integrin downstream regulator which is essential for fusion process. Collectively, our studies highlight the importance of down-regulation of COUP-TFII signaling to allow for the induction of factors crucial for myoblast fusion.
format	article
author	Hui-Ju Lee Chung-Yang Kao Shih-Chieh Lin Mafei Xu Xin Xie Sophia Y. Tsai Ming-Jer Tsai
author_facet	Hui-Ju Lee Chung-Yang Kao Shih-Chieh Lin Mafei Xu Xin Xie Sophia Y. Tsai Ming-Jer Tsai
author_sort	Hui-Ju Lee
title	Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development
title_short	Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development
title_full	Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development
title_fullStr	Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development
title_full_unstemmed	Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development
title_sort	dysregulation of nuclear receptor coup-tfii impairs skeletal muscle development
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f050c0d5eaa94eabad39bd6d6f06c5fd
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Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development

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