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Merck

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
RESUMEN

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.

MATERIALES
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Roche
Kit de detección de muerte celular in situ,TMR rojo, sufficient for ≤50 tests
Sigma-Aldrich
Anti-YAP1 (C-terminal) antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution