Loss of both GATA4 and GATA6 blocks cardiac myocyte differentiation and results in acardia in mice
Loss of both GATA4 and GATA6 blocks cardiac myocyte differentiation and results in acardia in mice
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DOI：
10.1016/j.ydbio.2008.03.013
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发表时间：
2008-05-15
影响因子：
2.7
通讯作者：
Duncan, Stephen A.
中科院分区：
文献类型：
--
作者：
Zhao, Roong;Watt, Alistair J.;Duncan, Stephen A.
尽管在识别诱导哺乳动物心脏发生的信号分子方面取得了重大进展，但控制心肌细胞基因表达的转录因子仍然难以捉摸。候选基因包括锌指转录因子GATA结合蛋白4和6 （GATA4, GATA6）。在小鼠中，由于胚胎外内胚层缺陷，任何一种蛋白质的个体缺失都会导致在心脏发育开始之前死亡；然而，当使用四倍体胚胎互补来规避这种胚胎外缺陷时，心肌细胞分化正常启动。在这里，我们表明这些因素在控制心肌细胞分化的开始有冗余的作用。作为一个Gata4(-/-)Gata6（-/-）胚胎完全没有心脏，尽管第二心区祖细胞仍然产生。我们的数据支持一个模型，即GATA4或GATA6对哺乳动物发育过程中调节心肌细胞基因表达的转录因子网络的表达至关重要。(C) 2008爱思唯尔公司所有航班预订。
Despite significant advances in identifying signaling molecules that induce cardiogenesis in mammals, the transcription factors that control the onset of cardiac myocyte gene expression have remained elusive. Candidates include the zinc finger transcription factors GATA binding proteins 4 and 6 (GATA4, GATA6). The individual loss of either protein in mice results in lethality prior to the onset of heart development due to defects in the extra-embryonic endoderm; however, when this extra-embryonic deficiency is circumvented using tetraploid embryo complementation, cardiac myrocyte differentiation initiates normally. Here we show that these factors have redundant roles in controlling the onset of cardiac myocyte differentiation. As a Gata4(-/-)Gata6(-/-) embryos completely lack hearts, although second heart field Progenitor cells are still generated. Our data support a model whereby GATA4 or GATA6 are essential for expression of the network of transcription factors that regulate the onset of cardiac myocyte gene expression during mammalian development. (C) 2008 Elsevier Inc. All Fights reserved.