T-box transcription factor Tbx2 represses differentiation and formation of the cardiac chambers
T-box transcription factor Tbx2 represses differentiation and formation of the cardiac chambers
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DOI：
10.1002/dvdy.10487
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发表时间：
2004-04-01
影响因子：
2.5
通讯作者：
Campione, M
中科院分区：
文献类型：
--
作者：
Christoffels, VM;Hoogaars, WMH;Campione, M
胚胎心管的特定区域分化为心房和心室心肌，而流入道，室内管道，内部弯曲和流出道没有。这些区域表达TBX2，一种转录阻遏物。在这里，我们测试了其在腔室形成中的作用。发现小鼠心脏中TBX2 mRNA和蛋白表达的时间和空间模式与室心肌特异性基因NPPA，CX40，CX43和凿子相互补，并且在人类中是保守的。在体外，TBX2抑制了CX40，CX43和NPPA的调节片段的活性。在预熟心肌中表达TBX2的转基因胚胎的心完全无法形成腔室，并表达室内心肌特异性基因NPPA，CX40和凿子，而其他心脏基因通常表达。这些发现提供了第一个证据，表明TBX2是局部抑制腔室特异性基因表达和腔室分化的决定因素。 （c）2004 Wiley-Liss，Inc。
Specific regions of the embryonic heart tube differentiate into atrial and ventricular chamber myocardium, whereas the inflow tract, atrioventricular canal, inner curvatures, and outflow tract do not. These regions express Tbx2, a transcriptional repressor. Here, we tested its role in chamber formation. The temporal and spatial pattern of Tbx2 mRNA and protein expression in mouse hearts was found to be complementary to that of chamber myocardium-specific genes Nppa, Cx40, Cx43, and Chisel, and was conserved in human. In vitro, Tbx2 repressed the activity of regulatory fragments of Cx40, Cx43, and Nppa. Hearts of transgenic embryos that expressed Tbx2 in the prechamber myocardium completely failed to form chambers and to express the chamber myocardium-specific genes Nppa, Cx40, and Chisel, whereas other cardiac genes were normally expressed. These findings provide the first evidence that Tbx2 is a determinant in the local repression of chamber-specific gene expression and chamber differentiation. (C) 2004 Wiley-Liss, Inc.