Retinoic acid (RA) is a vitamin A metabolite that acts as a morphogen and teratogen. Excess or defective RA signaling causes developmental defects including in the heart. The heart develops from the anterior lateral plate mesoderm. Cardiogenesis involves successive steps, including formation of the primitive heart tube, cardiac looping, septation, chamber development, coronary vascularization, and completion of the four‐chambered heart. RA is dispensable for primitive heart tube formation. Before looping, RA is required to define the anterior/posterior boundaries of the heart‐forming mesoderm as well as to form the atrium and sinus venosus. In outflow tract elongation and septation, RA signaling is required to maintain/differentiate cardiogenic progenitors in the second heart field at the posterior pharyngeal arches level. Epicardium‐secreted insulin‐like growth factor, the expression of which is regulated by hepatic mesoderm‐derived erythropoietin under the control of RA, promotes myocardial proliferation of the ventricular wall. Epicardium‐derived RA induces the expression of angiogenic factors in the myocardium to form the coronary vasculature. In cardiogenic events at different stages, properly controlled RA signaling is required to establish the functional heart.

中文翻译：

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维甲酸在心脏发育中的信号传导。

维甲酸（RA）是一种维生素A代谢产物，可作为形态发生剂和致畸剂。RA信号过多或缺陷会导致包括心脏在内的发育缺陷。心脏从前外侧板中胚层发育。心脏发生涉及连续的步骤，包括原始心管的形成，心脏环行，分隔，房室发育，冠状动脉血管形成和四腔心脏的完成。RA对于原始心脏管形成是必不可少的。循环之前，需要RA定义形成心脏的中胚层的前/后边界以及形成心房和窦静脉。在流出道延长和分隔中，需要RA信号以在咽后弓水平将第二心脏区域的心源性祖细胞维持/区分。心外膜分泌的胰岛素样生长因子，其表达受RA控制的中胚层来源的促红细胞生成素的调节，可促进心室壁的心肌增殖。心外膜来源的RA诱导心肌中血管生成因子的表达，从而形成冠状血管。在不同阶段的心源性事件中，需要适当控制的RA信号来建立功能性心脏。