Figure 3

Flii dysfunction results in myofibrillar architectural abnormalities of the ventricular myocardium.

(A–C) 3D volume renderings of maximum projections of Tg(myl7:LIFEACT-GFP) cardiac ventricles at 120 hpf from wild-type flii^+/+ (A), patient-specific flii^{R1230C/R1230C} (B), and flii^{D110fs/D110fs} (C); left panels show ventricular lumen; right panels show ventricular surface. Note that the complex trabecular network observed in wild-type is affected in both mutant alleles. In the severe loss-of-function flii^D110fs mutants, some of the epithelial shaped cardiomyocytes adopt a spherical shape and blebb out of the ventricular wall. Scale bars: 50 μm. Sample size for each genotype, n ≥ 3 biological replicates. (D–F) Representative TEM images of ventricular cardiac muscle from 120 hpf larvae, showing well-organized bundled myofibrils and z-discs in wild-type flii^+/+ (D), which are disorganized in patient-specific flii^{R1230C/R1230C} mutants (E) and appear to be more severely affected in flii^{D110fs/D110fs} mutants with faintly present z-discs (F). Yellow arrows, z-discs. Scale bars, 1 μm. Sample size for each genotype, n ≥ 3 biological replicates.