The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart
The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart
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DOI：
10.1016/j.cardiores.2004.01.030
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发表时间：
2004-06-01
影响因子：
10.8
通讯作者：
Christoffels, VM
中科院分区：
文献类型：
--
作者：
Hoogaars, WMH;Tessari, A;Christoffels, VM
目的：目前对调节传导系统形成的分子机制知之甚少。我们研究了发育的表达模式和功能方面的T-box转录因子Tbx 3，一种新的标记小鼠中枢传导系统（CCS）。研究方法：通过原位杂交和三维重建分析，在小鼠中分析了Tbx 3、Cx40、Cx43和Nppa的表达模式，这些标记物是发育心脏中心房和心室腔型心肌的标记物。体外研究Tbx 3对Nppa和Cx40启动子活性的调节作用。结果如下：在形成的心脏中，Tbx 3在窦房结（SAN）、房室结（AVN）、束支和近端束支（BB）以及结间区域和房室区域中表达。在整个心脏发育过程中，Tbx 3在从窦房结延伸到房室区域的不间断心肌域中表达。该表达结构域从E8.5开始存在于环状心管中。室型心肌标志物的表达特别地不存在于Tbx 3表达结构域中。Tbx 3能够抑制Nppa和Cx40启动子活性，并消除Tbx 5和Nkx2.5对Nppa启动子的协同激活。结论：T-box转录因子Tbx 3是一种新的中枢神经系统特异性标记物。我们的分析暗示了Tbx 3在抑制中枢传导系统的组成部分随后形成的区域中的基因表达的腔室特异性程序中的作用。(C)2004年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: The molecular mechanisms that regulate the formation of the conduction system are poorly understood. We studied the developmental expression pattern and functional aspects of the T-box transcription factor Tbx3, a novel marker for the murine central conduction system (CCS). Methods: The patterns of expression of Tbx3, and of Cx40, Cx43, and Nppa, which are markers for atrial and ventricular chamber-type myocardium in the developing heart, were analyzed in mice by in situ hybridization and three-dimensional reconstruction analysis. The function of Tbx3 in regulating Nppa and Cx40 promoter activity was Studied in vitro. Results: In the formed heart, Tbx3 is expressed in the sinoatrial node (SAN), atrioventricular node (AVN), bundle and proximal bundle branches (BBs), as well as the internodal regions and the atrioventricular region. Throughout cardiac development, Tbx3 is expressed in an uninterrupted myocardial domain that extends from the sinoatrial node to the atrioventricular region. This expression domain is present in the looping heart tube from E8.5 onwards. Expression of the chamber-type myocardial markers is specifically absent from the Tbx3 expression domain. Tbx3 is able to repress Nppa and Cx40 promoter activity and abolish the synergistic activation of the Nppa promoter by Tbx5 and Nkx2.5. Conclusion: We identified the T-box transcription factor Tbx3 as a novel and accurate marker for the central conduction system. Our analysis implicates a role for Tbx3 in repressing a chamber-specific program of gene expression in regions from which the components of the central conduction system are subsequently formed. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.