Pitx2 regulates cardiac left-right asymmetry by patterning second cardiac lineage-derived myocardium
Pitx2 regulates cardiac left-right asymmetry by patterning second cardiac lineage-derived myocardium
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DOI：
10.1016/j.ydbio.2006.06.009
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发表时间：
2006-08-15
影响因子：
2.7
通讯作者：
Martin, James F.
中科院分区：
文献类型：
--
作者：
Ai, Di;Liu, Wei;Martin, James F.
目前的左右不对称模型认为，早期的不对称信号是在节点处产生的，并通过节点信号分子的作用，以线性信号转导级联的方式传递到侧板中胚层。Pitx2同源盒基因在这个级联的最后阶段起作用，指导包括心脏在内的选定器官的不对称形态发生。我们之前的研究表明，Pitx2调节了一个独立于心脏环的不对称通路，这表明存在第二个不对称心脏通路。在心脏流出道中，Pitx2作为典型wnt信号的靶点，在心脏神经嵴和中胚层来源的心脏第二谱系中都起作用。我们使用命运定位、条件功能丧失和小鼠嵌合体分析来研究Pitx2在流出道形态发生中的作用。我们的研究结果表明，Pitx2在心脏神经嵴中是不可缺少的，但在第二系心肌中起作用，这表明该心脏祖细胞区是不对称的。(c) 2006爱思唯尔公司版权所有。
Current models of left-right asymmetry hold that an early asymmetric signal is generated at the node and transduced to lateral plate mesoderm in a linear signal transduction cascade through the function of the Nodal signaling molecule. The Pitx2 homeobox gene functions at the final stages of this cascade to direct asymmetric morphogenesis of selected organs including the heart. We previously showed that Pitx2 regulated an asymmetric pathway that was independent of cardiac looping suggesting a second asymmetric cardiac pathway. It has been proposed that in the cardiac outflow tract Pitx2 functions in both cardiac neural crest, as a target of canonical Wnt-signaling, and in the mesoderm-derived cardiac second lineage. We used fate mapping, conditional loss of function, and chimera analysis in mice to investigate the role of Pitx2 in outflow tract morphogenesis. Our findings reveal that Pitx2 is dispensable in the cardiac neural crest but functions in second lineage myocardium revealing that this cardiac progenitor field is patterned asymmetrically. (c) 2006 Elsevier Inc. All rights reserved.