Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis
Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis
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DOI：
10.1101/gad.11.8.1061
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发表时间：
1997-04-15
影响因子：
10.5
通讯作者：
Olson, EN
中科院分区：
文献类型：
--
作者：
Molkentin, JD;Lin, Q;Olson, EN
锌指转录因子GATA 4在心脏发育过程中的早期表达和激活心脏特异性基因表达的能力。为了确定GATA 4在胚胎发生中的作用，我们产生了GATA 4无效等位基因纯合子小鼠。纯合子GATA 4缺失小鼠在E7.0和E9.5之间由于严重的发育异常而发育停滞。突变胚胎最明显的缺乏一个原始的心管和前肠和部分卵黄囊外发展。在突变体中，两个双侧对称的前心肌原基未能向腹侧迁移，而是保持横向，并产生两个独立的心管，其中包含分化的心肌细胞。我们发现，这些畸形导致的一般损失，在整个胚胎的侧腹折叠。加塔$在前肠门后唇的心前内脏中胚层内表达最高，对应于经历腹侧融合的胚胎区域。我们建议，GATA 4所需的迁移或折叠形态发生的心前内脏中胚层细胞在AIP的水平。
The zinc finger transcription factor GATA4 has been implicated in heart development based on its early expression in precardiogenic splanchnic mesoderm and its ability to activate the expression of a number of cardiac-specific genes. To determine the role of GATA4 in embryogenesis, we generated mice homozygous for a GATA4 null allele. Homozygous GATA4 null mice arrested in development between E7.0 and E9.5 because of severe developmental abnormalities. Mutant embryos most notably lacked a primitive heart tube and foregut and developed partially outside the yolk sac. In the mutants, the two bilaterally symmetric promyocardial primordia failed to migrate ventrally but instead remained lateral and generated two independent heart tubes that contained differentiated cardiomyocytes. We show that these deformities resulted from a general loss in lateral to ventral folding throughout the embryo. GATA$ is most highly expressed within the precardiogenic splanchnic mesoderm at the posterior lip of the anterior intestinal portal, corresponding to the region of the embryo that undergoes ventral fusion. We propose that GATA4 is required for the migration or folding morphogenesis of the precardiogenic splanchnic mesodermal cells at the level of the AIP.