The mechanistic roles of Iroquois genes in embryonic heart development and physiology in zebrafish

Abstract

irx1a expression is found in the developing ventricle of the zebrafish embryos. irx1a morphants displayed phenotypes including dilated ventricle, pericardial effusion, pericardial edema and heart-looping defects. Electrocardiograms (ECGs) of the irx1a morphants showed a slower heart rate and a prolonged QT-interval resembling the phenotype of certain human congenital heart diseases. Arrhythmias were occasionally observed in the morphants. There is a down-regulation of irx2a, tbx5.1 and scn5Laa in the developing heart of the irx1a morphants. irx2a morphants and irx1a-and-irx2a-double-knockdown morphants displayed similar phenotypes and gene expression as shown in irx1a morphants. It suggested that the two iroquois genes may share similar roles in regulating cardiogenesis and cardiac functioning while irx2a is a potential downstream target of irx1a. Study using the zebrafish breakdance mutant proposed there is a regulatory relationship between kcnh2, irx1a and irx2a in a heart-specific pathway.