Teed off: cardiac conduction system development requires T-box transcription factors.
Teed off: cardiac conduction system development requires T-box transcription factors.
复制标题
开球：心脏传导系统的发育需要 T-box 转录因子。
DOI：
10.1161/circresaha.108.178061
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发表时间：
2008
影响因子：
20.1
通讯作者：
Yutzey,KatherineE
中科院分区：
文献类型：
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作者：
Yutzey,KatherineE
在本期的《循环研究》中，Bakker等报道了T-box转录因子Tbx3是小鼠房室传导系统发育所必需的。这项研究增加了T-box基因在发育中心脏细胞谱系成熟和增殖调节中日益复杂的作用。来自同一组的先前研究已经暗示Tbx3控制小鼠窦房结发育和起搏器活动。2一个密切相关的因子Tbx2也通过抑制心室肌中表达的基因而促进房室（AV）通道的特化。3，4人TBX5的突变导致Holt-Oram综合征，其包括传导系统疾病，并且具有Tbx5杂合突变的小鼠发展进行性AV阻滞和其他传导异常。5-7另外的T-box因子包括Tbx1、Tbx20和Tbx18在心脏的不同隔室中表达，并且在心脏细胞谱系成熟、增殖和形态发生中具有关键功能。越来越明显的是，多种T-box转录因子是传导系统分化和模式化的重要调节因子，同时也有助于心脏细胞谱系发育和形态发生的许多其他方面。Bakker等人1报道，基于小鼠功能丧失研究，Tbx3是房室传导系统成熟所必需的。缺乏Tbx3的小鼠不能存活超过胚胎日（E）14.5，并且在传导系统祖细胞中表现出异常的基因表达，以及严重的结构畸形，包括右心室双出口和室间隔缺损。特别注意室间隔的嵴，在那里将形成中央传导系统的AV束成分。在正常小鼠中，室间隔嵴中的肌细胞与间隔心肌的其余部分不同，Tbx3、Tbx5和Nkx2的表达增加。Cx43、Tbx18、Tbx20和心钠素（Nppa）的表达也明显降低。在缺乏Tbx3的小鼠中，Tbx18、Tbx20、Nppa和Cx40的表达增加在室间质嵴中是明显的。
In this issue of Circulation Research, Bakker et al1 report that the T-box transcription factor Tbx3 is required for development of the mouse atrioventricular conduction system. This study adds to the increasingly complex roles for T-box genes in the regulation of cell lineage maturation and proliferation in the developing heart. Previous studies from this same group have implicated Tbx3 in control of mouse sinoatrial node development and pacemaker activity. 2 A closely related factor Tbx2 also contributes to atrioventricular (AV) canal specification by repressing genes expressed in the chamber myocardium. 3, 4 Mutations in human TBX5 cause Holt–Oram syndrome, which includes conduction system disease, and mice with heterozygous mutations in Tbx5 develop progressive AV block and other conduction anomalies. 5–7 Additional T-box factors including Tbx1, Tbx20, and Tbx18 are expressed in distinct compartments of the heart and have critical functions in cardiac cell lineage maturation, proliferation, and morphogenesis. 8 It is becoming increasingly apparent that multiple T-box transcription factors are important regulators of conduction system differentiation and patterning while also contributing to many other aspects of heart cell lineage development and morphogenesis.Bakker et al1 report that Tbx3 is required for maturation of the atrioventricular conduction system based on loss of function studies in mice. Mice lacking Tbx3 do not survive past embryonic day (E) 14.5 and exhibit abnormal gene expression in conduction system progenitor cells, as well as severe structural malformations, including double outlet right ventricle and ventricular septal defects. Particular attention was paid to the crest of the interventricular septum, where the AV bundle components of the central conduction system will develop. In normal mice, the myocytes in the crest of the interventricular septum diversify from the rest of the septum myocardium with increased expression of Tbx3, Tbx5, and Nkx2. 5, as well decreased expression of connexin 43 (Cx43), Tbx18, Tbx20, and atrial natriuretic factor (Nppa). In the mice lacking Tbx3, increased expression of Tbx18, Tbx20, Nppa, and Cx40 is apparent in the crest of the interventricular