Tbx5 specifies the left/right ventricles and ventricular septum position during cardiogenesis
Tbx5 specifies the left/right ventricles and ventricular septum position during cardiogenesis
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DOI：
10.1242/dev.00797
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发表时间：
2003-12-01
期刊：
影响因子：
4.6
通讯作者：
Ogura, T
中科院分区：
文献类型：
--
作者：
Takeuchi, JK;Ohgi, M;Ogura, T
进行了广泛的错误表达研究，以探讨Tbx5所发挥的作用，其表达在心脏发生期间被排除在右心室（RV）之外。当Tbx5普遍错误表达时，室间隔不形成，导致单心室。在这样的心脏中，诱导左心室（LV）特异性ANF基因。在寻找推定的RV因子时，我们发现鸡Tbx20在RV中表达，显示出与Tbx5互补的方式。在Tbx5错误表达的心脏中，该基因被抑制。当错误表达是空间部分时，在右心室中留下小的Tbx5阴性区域，室间隔向右移位，导致小的RV和增大的LV。局灶性表达诱导Tbx5阳性和阴性区域在右心室，在那里形成一个额外的隔膜异位边界。从瞬时转基因小鼠中也获得了类似的结果。在这样的心脏中，dHAND和eHAND的表达模式随着明确的心脏异常而改变。此外，我们报告，人类ANF启动子是协同激活的Tbx5，Nkx2.5和GATA 4。这种激活被Tbx20废除，暗示了这些心脏特异性因子之间相互作用的关键作用。综上所述，我们的数据表明，Tbx5指定的LV通过几个心脏特异性因素之间的紧密相互作用的身份，并突出Tbx5在心脏发育中的重要作用。
Extensive misexpression studies were carried out to explore the roles played by Tbx5, the expression of which is excluded from the right ventricle (RV) during cardiogenesis. When Tbx5 was misexpressed ubiquitously, ventricular septum was not formed, resulting in a single ventricle. In such heart, left ventricle (LV)-specific ANF gene was induced. In search of the putative RV factor(s), we have found that chick Tbx20 is expressed in the RV, showing a complementary fashion to Tbx5. In the Tbx5-misexpressed heart, this gene was repressed. When misexpression was spatially partial, leaving small Tbx5-negative area in the right ventricle, ventricular septum was shifted rightwards, resulting in a small RV with an enlarged LV. Focal expression induced an ectopic boundary of Tbx5-positive and -negative regions in the right ventricle, at which an additional septum was formed. Similar results were obtained from the transient transgenic mice. In such hearts, expression patterns of dHAND and eHAND were changed with definitive cardiac abnormalities. Furthermore, we report that human ANF promoter is synergistically activated by Tbx5, Nkx2.5 and GATA4. This activation was abrogated by Tbx20, implicating the pivotal roles of interactions among these heart-specific factors. Taken together, our data indicate that Tbx5 specifies the identity of LV through tight interactions among several heart-specific factors, and highlight the essential roles of Tbx5 in cardiac development.