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Multiple Roles of Pitx2 in Cardiac Development and Disease

机译:Pitx2在心脏发育和疾病中的多重作用

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Cardiac development is a complex morphogenetic process initiated as bilateral cardiogenic mesoderm is specified at both sides of the gastrulating embryo. Soon thereafter, these cardiogenic cells fuse at the embryonic midline configuring a symmetrical linear cardiac tube. Left/right bilateral asymmetry is first detected in the forming heart as the cardiac tube bends to the right, and subsequently, atrial and ventricular chambers develop. Molecular signals emanating from the node confer distinct left/right signalling pathways that ultimately lead to activation of the homeobox transcription factor Pitx2 in the left side of distinct embryonic organ anlagen, including the developing heart. Asymmetric expression of Pitx2 has therefore been reported during different cardiac developmental stages, and genetic deletion of Pitx2 provided evidence of key regulatory roles of this transcription factor during cardiogenesis and thus congenital heart diseases. More recently, impaired Pitx2 function has also been linked to arrhythmogenic processes, providing novel roles in the adult heart. In this manuscript, we provide a state-of-the-art review of the fundamental roles of Pitx2 during cardiogenesis, arrhythmogenesis and its contribution to congenital heart diseases.
机译:心脏发育是一个复杂的形态发生过程,因为在胃胚胚胎的两侧都指定了双侧心源性中胚层。此后不久,这些心源性细胞在胚胎中线融合,构成对称的线性心导管。当心管向右弯曲时,首先在形成心脏的心脏中检测到左/右双侧不对称,然后,心房和心室发育。从节点发出的分子信号赋予了独特的左/右信号通路,最终导致了包括胚胎心脏在内的独特胚胎器官胶原蛋白左侧的同源盒转录因子Pitx2的激活。因此,在不同的心脏发育阶段已经报道了Pitx2的不对称表达,并且Pitx2的基因缺失提供了这种转录因子在心脏发生以及因此而来的先天性心脏病中的关键调节作用的证据。最近,Pitx2功能受损也与心律失常过程相关,在成年心脏中发挥了新作用。在此手稿中,我们提供了有关Pitx2在心脏发生,心律不齐及其在先天性心脏病中的作用的基本作用的最新综述。

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