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Merck
  • Yap1 is required for endothelial to mesenchymal transition of the atrioventricular cushion.

Yap1 is required for endothelial to mesenchymal transition of the atrioventricular cushion.

The Journal of biological chemistry (2014-05-17)
Hui Zhang, Alexander von Gise, Qiaozhen Liu, Tianyuan Hu, Xueying Tian, Lingjuan He, Wenjuan Pu, Xiuzhen Huang, Liang He, Chen-Leng Cai, Fernando D Camargo, William T Pu, Bin Zhou
要旨

Cardiac malformations due to aberrant development of the atrioventricular (AV) valves are among the most common forms of congenital heart diseases. Normally, heart valve mesenchyme is formed from an endothelial to mesenchymal transition (EMT) of endothelial cells of the endocardial cushions. Yes-associated protein 1 (YAP1) has been reported to regulate EMT in vitro, in addition to its known role as a major regulator of organ size and cell proliferation in vertebrates, leading us to hypothesize that YAP1 is required for heart valve development. We tested this hypothesis by conditional inactivation of YAP1 in endothelial cells and their derivatives. This resulted in markedly hypocellular endocardial cushions due to impaired formation of heart valve mesenchyme by EMT and to reduced endocardial cell proliferation. In endothelial cells, TGFβ induces nuclear localization of Smad2/3/4 complex, which activates expression of Snail, Twist1, and Slug, key transcription factors required for EMT. YAP1 interacts with this complex, and loss of YAP1 disrupts TGFβ-induced up-regulation of Snail, Twist1, and Slug. Together, our results identify a role of YAP1 in regulating EMT through modulation of TGFβ-Smad signaling and through proliferative activity during cardiac cushion development.

材料
製品番号
ブランド
製品内容

Roche
In Situ細胞死検出キット、TMRレッド, sufficient for ≤50 tests
Sigma-Aldrich
抗ホスホヒストンH3 (Ser10)抗体、有糸分裂マーカー, Upstate®, from rabbit
Sigma-Aldrich
クロマチン免疫沈降(ChIP)アッセイキット, Contains all necessary reagents to perform 22 individual chromatin immunoprecipitation (ChIP) reactions using inexpensive protein A agarose beads.
Sigma-Aldrich
抗YAP1 (C-末端) ウサギ宿主抗体, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution