A basic helix‐loop‐helix transcription factor Hey2 is expressed in the ventricular myocardium and endocardium of mouse embryos, and Hey2 null mice die perinatally showing ventricular septal defect, dysplastic tricuspid valve and hypoplastic right ventricle. In order to understand region‐specific roles of Hey2 during cardiac morphogenesis, we generated Hey2 conditional knockout (cKO) mice using Mef2c‐AHF‐Cre, which was active in the anterior part of the second heart field and the right ventricle and outflow tract of the heart. Hey2 cKO neonates reproduced three anomalies commonly observed in Hey2 null mice. An earliest morphological defect was the lack of right ventricular extension along the apico‐basal axis at midgestational stages. Underdevelopment of the right ventricle was present in all cKO neonates including those without apparent atresia of right‐sided atrioventricular connection. RNA sequencing analysis of cKO embryos identified that the gene expression of a non‐chamber T‐box factor Tbx2 was ectopically induced in the chamber myocardium of the right ventricle. Consistently, mRNA expression of the Mycn transcription factor, which was a cell cycle regulator transcriptionally repressed by Tbx2, was down regulated, and the number of S‐phase cells was significantly decreased in the right ventricle of cKO heart. These results suggest that Hey2 plays an important role in right ventricle development during cardiac morphogenesis, at least in part, through mitigating Tbx2‐dependent inhibition of Mycn expression.

中文翻译：

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Hey2 转录因子在心脏形态发生过程中通过调节 Tbx2-Mycn 通路在右心室发育中的作用

一种基本的螺旋-环-螺旋转录因子 Hey2 在小鼠胚胎的心室心肌和心内膜中表达，Hey2缺失小鼠在围产期死亡时表现出室间隔缺损、发育不良的三尖瓣和发育不良的右心室。为了了解 Hey2 在心脏形态发生过程中的区域特异性作用，我们使用Mef2c-AHF-Cre生成了Hey2条件敲除 (cKO) 小鼠，其在第二心场的前部以及右心室和流出道中活跃。心脏。Hey2 cKO 新生儿再现了Hey2 中常见的三种异常空老鼠。最早的形态学缺陷是在妊娠中期缺乏沿心尖-基底轴的右心室伸展。所有 cKO 新生儿都存在右心室发育不全，包括那些没有明显右侧房室连接闭锁的新生儿。cKO 胚胎的 RNA 测序分析发现，非腔室 T-box 因子 Tbx2 的基因表达在右心室的腔室心肌中被异位诱导。一致地，Mycn 转录因子（一种被 Tbx2 转录抑制的细胞周期调节因子）的 mRNA 表达下调，并且 cKO 心脏右心室中 S 期细胞的数量显着减少。这些结果表明 Hey2 在心脏形态发生过程中在右心室发育中起重要作用，Mycn表达式。