Abstract
Cardiac development is a complex process that is strictly controlled by various factors, including PcG protein complexes. Several studies have reported the critical role of PRC2 in cardiogenesis. However, little is known about the regulation mechanism of PRC1 in embryonic heart development. To gain more insight into the mechanistic role of PRC1 in cardiogenesis, we generated a PRC1 loss-of-function zebrafish line by using the CRISPR/Cas9 system targeting rnf2, a gene encoding the core subunit shared by all PRC1 subfamilies. Our results revealed that Rnf2 is not involved in cardiomyocyte differentiation and heart tube formation, but that it is crucial to maintaining regular cardiac contraction. Further analysis suggested that Rnf2 loss-of-function disrupted cardiac sarcomere assembly through the ectopic activation of non-cardiac sarcomere genes in the developing heart. Meanwhile, Rnf2 deficiency disrupts the construction of the atrioventricular canal and the sinoatrial node by modulating the expression of bmp4 and other atrioventricular canal marker genes, leading to an impaired cardiac conduction system. The disorganized cardiac sarcomere and defective cardiac conduction system together contribute to defective cardiac contraction. Our results emphasize the critical role of PRC1 in the cardiac development.
Highlights
At 72 hpf, rnf2−/− embryos exhibited pleiotropic phenotypes, including defective craniofacial structures, small eyes, missing pectoral fins and clear pericardial edema encompassing a stringy heart with weak contractility (Figures 1D,E and S1), which was consistent with previous reports [29,30,31]
Unlike the heart of the wild-type embryos, which displayed a constrictive atrioventricular canal (AVC) between the atrial and ventricular chambers and protruded well-formed primitive valve leaflets, the AVCs of the rnf2−/− embryos were less constricted and the primitive valve leaflets were missing (Figure 1F). These results suggested that the formation of the AVC and primitive valves are severely disrupted in rnf2−/− embryos
Our results suggested that Rnf2 helps to generate proper cardiac contraction by regulating the expression of genes associated with cardiac sarcomere assembly and the cardiac conduction system
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. As the first organ to generate and function in the embryo, heart development is strictly regulated by various molecules and signal pathways. To become mature and functional, the embryonic heart undergoes a series of complex processes, including the specification and differentiation of cardiac lineages, the morphogenesis of the heart tube, looping, the assembly of cardiac chambers, the constriction of the atrioventricular canal, and the establishment of proper cardiac functions [1,2,3]. Errors in any of these processes can cause congenital heart malformations [4,5]
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