Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18
Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18
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DOI：
10.1161/01.res.0000227571.84189.65
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发表时间：
2006-06-23
影响因子：
20.1
通讯作者：
Kispert, Andreas
中科院分区：
文献类型：
--
作者：
Christoffels, Vincent M.;Mommersteeg, Mathilda T. M.;Kispert, Andreas
哺乳动物心脏的静脉极是一个结构和电学复杂的区域，但其形成的谱系和分子机制仍在很大程度上未被探索。与将心肌窦角的起源归因于胚胎静脉极的经典研究相反，我们发现窦角仅在心脏循环后由横隔区域的间充质细胞分化为心肌形成。心肌窦角及其间充质前体细胞从不表达Nkx2 - 5，这是一种对心脏发育至关重要的转录因子。此外，谱系研究表明，窦角并不来源于先前对Nkx 2 - 5呈阳性的细胞。相反，窦角表达T-box转录因子基因Tbx18。Tbx18缺陷的小鼠不能从心包间充质形成窦角，并且具有缺陷的腔静脉，而肺静脉和心房结构不受影响。我们的研究定义了一种新的心脏前体细胞群，其专门贡献于发育中心脏的窦角或全身静脉支流周围的心肌，这是先天性畸形和心律失常的来源。
The venous pole of the mammalian heart is a structurally and electrically complex region, yet the lineage and molecular mechanisms underlying its formation have remained largely unexplored. In contrast to classical studies that attribute the origin of the myocardial sinus horns to the embryonic venous pole, we find that the sinus horns form only after heart looping by differentiation of mesenchymal cells of the septum transversum region into myocardium. The myocardial sinus horns and their mesenchymal precursor cells never express Nkx2-5, a transcription factor critical for heart development. In addition, lineage studies show that the sinus horns do not derive from cells previously positive for Nkx2-5. In contrast, the sinus horns express the T-box transcription factor gene Tbx18. Mice deficient for Tbx18 fail to form sinus horns from the pericardial mesenchyme and have defective caval veins, whereas the pulmonary vein and atrial structures are unaffected. Our studies define a novel heart precursor population that contributes exclusively to the myocardium surrounding the sinus horns or systemic venous tributaries of the developing heart, which are a source of congenital malformation and cardiac arrhythmias.