Nkx genes regulate heart tube extension and exert differential effects on ventricular and atrial cell number.
Nkx genes regulate heart tube extension and exert differential effects on ventricular and atrial cell number.
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DOI：
10.1016/j.ydbio.2008.07.037
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发表时间：
2008-10-15
影响因子：
2.7
通讯作者：
Yelon, Deborah
中科院分区：
文献类型：
--
作者：
Targoff, Kimara L.;Schell, Thomas;Yelon, Deborah
心脏的形成是一个复杂的形态发生过程，心脏形态发生的紊乱会导致先天性心脏病。NKX 2 -5是与心脏出生缺陷相关的关键致病基因，可能是因为其在心脏发生的早期步骤中发挥重要作用。先前在模式生物中的研究涉及NKX 2 -5同源物在许多过程中，包括心脏祖细胞特化，祖细胞增殖和室形态发生。通过抑制斑马鱼NKX 2 -5同源物nkx2.5和nkx2.7的功能，我们表明nkx基因对于建立线性心管的原始尺寸是必需的。nkx缺陷的心管不能正常伸长：心室部分短而宽，心房部分杂乱无章。这种心房表型与心房心肌细胞过剩有关，而心室细胞数量在此阶段正常。然而，在nkx缺陷的胚胎发育后期，当心脏腔出现时，心室细胞数量减少。因此，我们得出结论，nkx基因调节心管的延伸，并发挥不同的影响心室和心房细胞的数量。我们的数据表明，在NKX 2 -5突变的患者中，形态发生错误可能起源于心管组装的早期阶段。
Heart formation is a complex morphogenetic process, and perturbations in cardiac morphogenesis lead to congenital heart disease. NKX2-5 is a key causative gene associated with cardiac birth defects, presumably because of its essential roles during the early steps of cardiogenesis. Previous studies in model organisms implicate NKX2-5 homologs in numerous processes, including cardiac progenitor specification, progenitor proliferation, and chamber morphogenesis. By inhibiting function of the zebrafish NKX2-5 homologs, nkx2.5 and nkx2.7, we show that nkx genes are essential to establish the original dimensions of the linear heart tube. The nkx-deficient heart tube fails to elongate normally: its ventricular portion is atypically short and wide, and its atrial portion is disorganized and sprawling. This atrial phenotype is associated with a surplus of atrial cardiomyocytes, whereas ventricular cell number is normal at this stage. However, ventricular cell number is decreased in nkx-deficient embryos later in development, when cardiac chambers are emerging. Thus, we conclude that nkx genes regulate heart tube extension and exert differential effects on ventricular and atrial cell number. Our data suggest that morphogenetic errors could originate during early stages of heart tube assembly in patients with NKX2-5 mutations.
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DOI：
10.1073/pnas.97.22.11984
发表时间：
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影响因子：
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