Fig. S6

Sarcomeric defects within cct3^sa1761 are not predominantly caused by deficiencies in myosin folding and retina degeneration characterizes cct1^hi3564Tg, cct2^hi1269Tg, cct8^mn30Gt and cct4^-14. Related to Figures 3 and 4. (A) Administration of 10 μM EMD57033, a small molecule that stabilizes and refolds myosin (Radke et al., 2014), significantly increased the birefringence of 3-dpf-old wildtype larvae compared to DMSOtreated control embryos. No significant effect was observed with 1 μM EMD57033 and administration of 100 μM EMD57033 was lethal. Data are mean ± SEM; *p < 0.05 by one-way ANOVA with Tukey’s post hoc test; n = 10. (B) Compared to 3-dpf-old wildtype larvae that were injected with 300 μM standard control morpholino and treated with the control vehicle DMSO at 1 dpf, administration of 300 μM unc45b morpholino and subsequent DMSO treatment led to a highly significant reduction in birefringence. Treatment of unc45b morphants with 10 μM EMD57033 at 1 dpf led to a highly significant amelioration of the birefringence compared to DMSO-treated unc45b morphants. Data are mean ± SEM; ****p < 0.0001 by one-way ANOVA with Tukey’s post hoc test; n = 20. (C) Administration of 10 μM EMD57033 did not significantly (n. s.) ameliorate the birefringence of cct3^sa1761 homozygotes. Data are mean ± SEM; *p < 0.05 by one-way ANOVA with Tukey’s post hoc test; n = 10. (D-G) H&E-stained sections of 3-dpf-old larvae revealed retina degeneration in the following mutants. Representatives of a minimum of 6 analyzed larvae per genotype are shown (n > 6 per genotype). (D) Homozygotes of gene trap mutant cct1^hi3564Tg. (E) Homozygotes of gene trap mutant cct2^hi1269Tg. (F) Homozygotes of gene trap mutant cct8^mn30Gt. (G) Homozygotes of null mutant cct4^-14.