Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development

Hui Ju Lee, Chung Yang Kao, Shih-Chieh Lin, Mafei Xu, Xin Xie, Sophia Y. Tsai, Ming Jer Tsai

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Article number3136
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

Fingerprint

COUP Transcription Factor II
Muscle Development
Cytoplasmic and Nuclear Receptors
Skeletal Muscle
Cell Fusion
Myoblasts
Muscle Cells
Down-Regulation
Focal Adhesion Protein-Tyrosine Kinases
Integrins
Cell Differentiation

All Science Journal Classification (ASJC) codes

  • General

Cite this

Lee, Hui Ju ; Kao, Chung Yang ; Lin, Shih-Chieh ; Xu, Mafei ; Xie, Xin ; Tsai, Sophia Y. ; Tsai, Ming Jer. / Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development. In: Scientific reports. 2017 ; Vol. 7, No. 1.
@article{e9ee327db4eb40cf85261024c5a96c04,
title = "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 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.",
author = "Lee, {Hui Ju} and Kao, {Chung Yang} and Shih-Chieh Lin and Mafei Xu and Xin Xie and Tsai, {Sophia Y.} and Tsai, {Ming Jer}",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-03475-5",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development. / Lee, Hui Ju; Kao, Chung Yang; Lin, Shih-Chieh; Xu, Mafei; Xie, Xin; Tsai, Sophia Y.; Tsai, Ming Jer.

In: Scientific reports, Vol. 7, No. 1, 3136, 01.12.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dysregulation of nuclear receptor COUP-TFII impairs skeletal muscle development

AU - Lee, Hui Ju

AU - Kao, Chung Yang

AU - Lin, Shih-Chieh

AU - Xu, Mafei

AU - Xie, Xin

AU - Tsai, Sophia Y.

AU - Tsai, Ming Jer

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85020680905&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020680905&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-03475-5

DO - 10.1038/s41598-017-03475-5

M3 - Article

C2 - 28600496

AN - SCOPUS:85020680905

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 3136

ER -