Hesr1 and Hesr2 regulate atrioventricular boundary formation in the developing heart through the repression of Tbx2
Hesr1 and Hesr2 regulate atrioventricular boundary formation in the developing heart through the repression of Tbx2
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DOI：
10.1242/dev.02777
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发表时间：
2007-02-15
期刊：
影响因子：
4.6
通讯作者：
Saga, Yumiko
中科院分区：
文献类型：
--
作者：
Kokubo, Hiroki;Tomita-Miyagawa, Sachiko;Saga, Yumiko
心室特异性的建立是心脏形态发生和功能的基本要求。Hesr1 （Hey1）和Hesr2 （Hey2）分别在心房和心室特异性表达，暗示这些基因参与了心室规范。在我们目前的研究中，我们发现Hesr1或Hesr2在小鼠整个心脏谱系中的强制表达会导致房室（AV）管的减少或丧失。在hesr1错误表达的心脏中，房室管边界不明确，房室心肌特异性标志物Bmp2和Tbx2的表达水平非常弱或无法检测到。在hesr2错误表达的胚胎中观察到更有效的影响，其中房室管似乎完全缺失。这些数据表明，Hesr1和Hesr2可能阻止细胞表达导致AV边界精确形成的AV通道特异性基因。我们的研究结果表明，Tbx2的表达可能直接受到Hesr1和Hesr2的抑制。此外，我们发现Hesr1和Hesr2的表达不依赖于Notch2信号。综上所述，我们的数据表明，Hesr1和Hesr2通过抑制Tbx2在AV边界形成中发挥关键作用。
The establishment of chamber specificity is an essential requirement for cardiac morphogenesis and function. Hesr1 (Hey1) and Hesr2 (Hey2) are specifically expressed in the atrium and ventricle, respectively, implicating these genes in chamber specification. In our current study, we show that the forced expression of Hesr1 or Hesr2 in the entire cardiac lineage of the mouse results in the reduction or loss of the atrioventricular (AV) canal. In the Hesr1-misexpressing heart, the boundaries of the AV canal are poorly defined, and the expression levels of specific markers of the AV myocardium, Bmp2 and Tbx2, are either very weak or undetectable. More potent effects were observed in Hesr2-misexpressing embryos, in which the AV canal appears to be absent entirely. These data suggest that Hesr1 and Hesr2 may prevent cells from expressing the AV canal-specific genes that lead to the precise formation of the AV boundary. Our findings suggest that Tbx2 expression might be directly suppressed by Hesr1 and Hesr2. Furthermore, we find that the expression of Hesr1 and Hesr2 is independent of Notch2 signaling. Taken together, our data demonstrate that Hesr1 and Hesr2 play crucial roles in AV boundary formation through the suppression of Tbx2.