Abstract：
Formation of the vertebrate heart with its complex arterial and venous connections is critically dependent on patterning of the left-right axis during early embryonic development. Abnormalities in left-right patterning can lead to a variety of complex life-threatening congenital heart defects. A highly conserved pathway responsible for left-right axis specification has been uncovered. This pathway involves initial asymmetric activation of a nodal signaling cascade at the embryonic node, followed by its propagation to the left lateral plate mesoderm and activation of left-sided expression of the Pitx2 transcription factor specifying visceral organ asymmetry. Intriguingly, recent work suggests that cardiac laterality is encoded by intrinsic cell and tissue chirality independent of Nodal signaling. Thus, Nodal signaling may be superimposed on this intrinsic chirality, providing additional instructive cues to pattern cardiac situs. The impact of intrinsic chirality and the perturbation of left-right patterning on myofiber organization and cardiac function warrants further investigation. We summarize recent insights gained from studies in animal models and also some human clinical studies in a brief overview of the complex processes regulating cardiac asymmetry and their impact on cardiac function and the pathogenesis of congenital heart defects.
摘要：
具有复杂的动脉和静脉连接的脊椎动物心脏的形成在很大程度上取决于早期胚胎发育过程中左右轴的模式。左右模式的异常可导致各种复杂的危及生命的先天性心脏缺陷。已经发现了负责左右轴规格的高度保守的途径。该途径涉及胚胎节点的节点信号级联的初始不对称激活，随后传播到左外侧板中胚层，并激活指定内脏器官不对称性的Pitx2转录因子的左侧表达。有趣的是，最近的研究表明,心脏侧向性是由固有的细胞和组织手性编码的,不依赖于Nodal信号传导.因此，节点信令可以叠加在这种固有的手性上，提供额外的指导性线索来图案化心脏位置。内在手性和左右模式的扰动对肌纤维组织和心脏功能的影响值得进一步研究。我们总结了从动物模型研究以及一些人类临床研究中获得的最新见解，简要概述了调节心脏不对称的复杂过程及其对心脏功能和先天性心脏缺陷发病机理的影响。
