MYOGENIC AND MORPHOGENETIC DEFECTS IN THE HEART TUBES OF MURINE EMBRYOS LACKING THE HOMEO BOX GENE NKX2-5
MYOGENIC AND MORPHOGENETIC DEFECTS IN THE HEART TUBES OF MURINE EMBRYOS LACKING THE HOMEO BOX GENE NKX2-5
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DOI：
10.1101/gad.9.13.1654
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发表时间：
1995-07-01
影响因子：
10.5
通讯作者：
HARVEY, RP
中科院分区：
文献类型：
--
作者：
LYONS, I;PARSONS, LM;HARVEY, RP
小鼠同源盒基因Nkx2-5在心脏前中胚层以及胚胎和胎儿心脏的心肌中表达。靶向阻断Nkx2-5导致心脏形态发生异常、生长迟缓和胚胎死亡，与性交后9-10天相似。在突变的胚胎中，心管的形成是正常的，但在线性心管阶段(8.25-8.5d P.C.)，心脏形态的关键决定因素--环状形态发生并不启动。对心肌谱系的承诺、大多数肌丝基因的表达和肌原纤维的形成都没有受到影响。然而，肌球蛋白轻链2V基因(MLC2V)在突变的心脏和突变的ES细胞来源的心肌细胞中不表达。MLC2V的表达通常只出现在心室细胞中，是已知的最早的心室分化分子标志物。另外两个心室标志物肌球蛋白重链β和细胞周期蛋白D2在突变心脏中的局部表达表明，并不是所有的心室特异基因表达都依赖于Nkx2-5。这些数据表明，Nkx2-5对于正常的心脏形态发生、肌肉发生和功能是必不可少的。此外，该基因是脑室肌源性特化所需的遗传途径的组成部分。
The murine homeo box gene Nkx2-5 is expressed in precardiac mesoderm and in the myocardium of embryonic and fetal hearts. Targeted interruption of Nkx2-5 resulted in abnormal heart morphogenesis, growth retardation and embryonic lethality at similar to 9-10 days postcoitum (p.c.). Heart tube formation occurred normally in mutant embryos, but looping morphogenesis, a critical determinant of heart form, was not initiated at the linear heart tube stage (8.25-8.5 days p.c.). Commitment to the cardiac muscle lineage, expression of most myofilament genes and myofibrillogenesis were not compromised. However, the myosin light-chain 2V gene (MLC2V) was not expressed in mutant hearts nor in mutant ES cell-derived cardiocytes. MLC2V expression normally occurs only in ventricular cells and is the earliest known molecular marker of ventricular differentiation. The regional expression in mutant hearts of two other ventricular markers, myosin heavy-chain beta and cyclin D2, indicated that not all ventricle-specific gene expression is dependent on Nkx2-5. The data demonstrate that Nkx2-5 is essential for normal heart morphogenesis, myogenesis, and function. furthermore, this gene is a component of a genetic pathway required for myogenic specialization of the ventricles.