Scientists Reveal Novel Function of YAP1 in Endothelial to Mesenchymal Transition of the Atrioventricular Cushion
Jun 23, 2014 Email"> PrintText Size
Research group led by Professor ZHOU Bin, at the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences found that YAP1 in the Hippo signaling pathway could cooperate with TGFb/Smad signaling pathway to regulate the Endothelial to Mesenchymal Transition (EMT) of the Atrioventricular Cushion during embryonic heart development.
Aberrant cushion development is thought to be involved in the pathogenesis of various types of congenital heart disease (CHD), which is a major cause of death in infancy. Understanding the cardiac cushion development and underlying molecular mechanisms will give insights to the treatment and precaution of CHD.
In their study, Dr. ZHOU and his colleagues used transgenic mouse Tie2-Cre to specifically delete YAP1 gene in endocardium, which resulted in markedly hypocellular endocardial cushion at embryonic day 9.5. They proved this phenotype was due to impaired formation of heart valve mesenchyme by EMT through lineage tracing and tissue culture experiments.
Furthermore, they demonstrated the expression of Snail, Slug and Twist1 in mutant cushions was down regulated via in situ hybridization and real-time PCR assays. Snail, Slug and Twist1, which play important roles in regulating cardiac cushion EMT, are downstream targets of TGFb/Smad pathway. In endothelial cells, YAP1 could interact with Smad2/3/4 complex and regulate its nuclear localization. Thus loss of YAP1 disrupts TGFb induced upregulation of Snail, Slug and Twist1.
YAP1 is an important regulator for cell proliferation and organ size. Previous study has showed the effect of YAP1 on EMT of cell lines in vitro. This study is the first time to demonstrate the role of YAP1 in EMT during cardiac cushion development in vivo.
This work entitled “Yap1 is required for endothelial to mesenchymal transition of the atrioventricular cushion” was published in The Journal of Biological Chemistry on May 15, 2014.
The study was funded by grants from Ministry of Science and Technology of China, the Natural Science Foundation of China and Chinese Academy of Sciences.
Figure 1. Lineage tracing experiment showed reduced EMT ability of endothelial cells of YAP1 mutant. (Image by Dr. ZHOU Bin's Group)
Contact:
ZHOU Bin, Ph.D., Principal Investigator
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,
Shanghai 200031, China.
Tel: 86-21-54920974;
Fax: 86-21-54920291;
E-mail: zhoubin@sibs.ac.cn
Research group led by Professor ZHOU Bin, at the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences found that YAP1 in the Hippo signaling pathway could cooperate with TGFb/Smad signaling pathway to regulate the Endothelial to Mesenchymal Transition (EMT) of the Atrioventricular Cushion during embryonic heart development.
Aberrant cushion development is thought to be involved in the pathogenesis of various types of congenital heart disease (CHD), which is a major cause of death in infancy. Understanding the cardiac cushion development and underlying molecular mechanisms will give insights to the treatment and precaution of CHD.
In their study, Dr. ZHOU and his colleagues used transgenic mouse Tie2-Cre to specifically delete YAP1 gene in endocardium, which resulted in markedly hypocellular endocardial cushion at embryonic day 9.5. They proved this phenotype was due to impaired formation of heart valve mesenchyme by EMT through lineage tracing and tissue culture experiments.
Furthermore, they demonstrated the expression of Snail, Slug and Twist1 in mutant cushions was down regulated via in situ hybridization and real-time PCR assays. Snail, Slug and Twist1, which play important roles in regulating cardiac cushion EMT, are downstream targets of TGFb/Smad pathway. In endothelial cells, YAP1 could interact with Smad2/3/4 complex and regulate its nuclear localization. Thus loss of YAP1 disrupts TGFb induced upregulation of Snail, Slug and Twist1.
YAP1 is an important regulator for cell proliferation and organ size. Previous study has showed the effect of YAP1 on EMT of cell lines in vitro. This study is the first time to demonstrate the role of YAP1 in EMT during cardiac cushion development in vivo.
This work entitled “Yap1 is required for endothelial to mesenchymal transition of the atrioventricular cushion” was published in The Journal of Biological Chemistry on May 15, 2014.
The study was funded by grants from Ministry of Science and Technology of China, the Natural Science Foundation of China and Chinese Academy of Sciences.
Figure 1. Lineage tracing experiment showed reduced EMT ability of endothelial cells of YAP1 mutant. (Image by Dr. ZHOU Bin's Group)
Contact:
ZHOU Bin, Ph.D., Principal Investigator
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,
Shanghai 200031, China.
Tel: 86-21-54920974;
Fax: 86-21-54920291;
E-mail: zhoubin@sibs.ac.cn
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