Tbx20 is essential for cardiac chamber differentiation and repression of Tbx2

被引:158
作者
Singh, MK
Christoffels, VM
Dias, JM
Trowe, MO
Petry, M
Schuster-Gossler, K
Bürger, A
Ericson, J
Kispert, A [1 ]
机构
[1] Hannover Med Sch, Inst Mol Biol, D-30625 Hannover, Germany
[2] Univ Amsterdam, Acad Med Ctr, Dept Anat & Embryol, NL-1105 AZ Amsterdam, Netherlands
[3] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden
来源
DEVELOPMENT | 2005年 / 132卷 / 12期
关键词
T-box; heart; myocardium; anterior heart field; Bmp;
D O I
10.1242/dev.01854
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Tbx20, a member of the T-box family of transcriptional regulators, shows evolutionary conserved expression in the developing heart. In the mouse, Tbx20 is expressed in the cardiac crescent, then in the endocardium and myocardium of the linear and looped heart tube before it is restricted to the atrioventricular canal and outflow tract in the multi-chambered heart. Here, we show that TWO is required for progression from the linear heart tube to a multi-chambered heart. Mice carrying a targeted mutation of Tbx20 show early embryonic lethality due to hemodynamic failure. A linear heart tube with normal anteroposterior patterning is established in the mutant. The tube does not elongate, indicating a defect in recruitment of mesenchyme from the secondary heart field, even though markers of the secondary heart field are not affected. Furthermore, dorsoventral patterning of the tube, formation of working myocardium, looping, and further differentiation and morphogenesis fail. Instead, Tbx2, Bmp2 and vinexin alpha (Sh3d4), genes normally restricted to regions of primary myocardium and lining endocardium, are ectopically expressed in the linear heart tube of Tbx2O mutant embryos. Because Tbx2 is both necessary and sufficient to repress chamber differentiation (Christoffels et a]., 2004a; Harrelson et al., 2004), Tbx20 may ensure progression to a multi-chambered heart by repressing Tbx2 in the myocardial precursor cells of the linear he-art tube destined to form the chambers.
引用
收藏
页码:2697 / 2707
页数:11
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