Inhibition of miR-143 biosynthesis results in structural malformations of the cardiac chambers and decreased cardiac function. (A) Northern analysis. No mature miR-143 can be visualized in MO143 zebrafish embryos, whereas miR-145 expression appears unaltered. (B-E) Inhibition of miR-143 biosynthesis results in ventricular collapse and atrial dilation. Lateral views (anterior to the right) are shown of control and MO143-injected Tg(cmlc2::GFP) embryos at 48 hpf imaged under transmitted (B,D) and fluorescent (C,E) light. Arrowhead in D indicates pericardial edema. (F-K) Inhibition of miR-143 compromises ventricular function between 36 and 48 hpf. (F) The percentage of animals with a contractile defect at 48 hpf elicited by three independent morpholinos. DVC, decreased ventricular contractility (red); MON, monster (alive but severely deformed and not accurately scorable for the heart defect; yellow); WT, wild type (blue). (G) Contractility as percentage fractional shortening (FS%) in WT and MO143 hearts at 36 and 48 hpf. *, P=8.03x10-15; error bars represent ± s.e.m. (H-K) Microangiography of WT and MO143 embryos at 36 and 48 hpf. Arrowheads indicate circulating beads in the head and trunk. Red, beads; green, myocardium.
|