FIGURE SUMMARY
Title

Human cardiomyopathy mutations induce myocyte hyperplasia and activate hypertrophic pathways during cardiogenesis in zebrafish

Authors
Becker, J.R., Deo, R.C., Werdich, A.A., Panàkovà, D., Coy, S., and MacRae, C.A.
Source
Full text @ Dis. Model. Mech.
Fig. 2

TNNT2sp morphants have reduced ventricular dimensions and impaired ventricular function. (A) Comparison of control-injected (top) and TNNT2sp morphant (bottom) embryos at 96 hpf. (B) Representative high-magnification image of control (left) and TNNT2sp morphant (right) heart (A, atria; V, ventricle; atria not visible in control). (C) Chamber dimensions in control (black bar) and TNNT2sp morphants (gray bar). (D) FS in control (black bar) and TNNT2sp morphants (gray bar). *P<0.05; n=5 for all measurements. All data expressed as mean + s.e.m.

PHENOTYPE:
Fish:
Knockdown Reagent:
Observed In:
Stage: Day 4
Fig. 3

Disruption of sarcomere structure and induction of myocardial hyperplasia in TNNT2sp morphants. (A) Representative electron micrographs of 96 hpf (top), 8 dpf (middle) and 21 dpf (bottom) ventricular cardiomyocytes. (B) Total cardiomyocytes at 48 hpf and 96 hpf. (C) Cardiomyocyte area at 96 hpf. *P<0.05; n=3–5 hearts per time point. All data expressed as mean + s.e.m.
Fig. 4

Distinct alterations in Ca2+ handling induced by altered TNNT2 splicing. Diastolic (A) and transient amplitude (B) Ca2+ measurements in specific heart regions in controls, TNNT2sp morphants and TNNTatg (null) morphants. (C) CTD50 measured in atrium, atrioventricular canal (AVC), outer ventricular curvature (OC), mid-ventricle (MV) and inner ventricular curvature (IC). Asterisk donates P<0.05 for comparison of TNNT2sp morphant with control sample, or TNNT2atg morphant with control. All data expressed as mean ± s.e.m.
Fig. 5

Altered tnnt2 splicing induces significant changes in the expression of sarcomeric genes, neurohormonal genes and markers of hypertrophy. (A) Expression profiling identifies upregulation of myh6 (black bar) and confirms efficacy of TNNT2sp MO [white bar labeled ′tnnt2 (Exon 13)′. (B) Genes involved in cardiomyocyte Ca2+ handling that are differentially regulated in TNNT2sp morphants. (C) Pathway analysis identifies significant downregulation of expression of genes encoding specific hormones - ghrh, pth1a, pomca and uts2a. (D) qPCR confirmation of select up- and downregulated genes. All data expressed as mean + s.e.m.

PHENOTYPE:
Fish:
Knockdown Reagent:
Observed In:
Stage: Day 4
Acknowledgments
This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Dis. Model. Mech.
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