Fig. 7

Circadian clock genes are part of the nphp8 genetic network controlling the ciliopathy-specific phenotypes. (A) Differential expression studies of nphp8^sa24730 mutants and control siblings identified the circadian clock genes cry1a, cry5 and per2 as upregulated in the nphp8 mutants. (B) Depletion of cry1a and cry5 in Tg(wt1b:GFP; cdh17:GFP) embryos with two different MO each (SBM and TBM) significantly increased the frequency of glomerular cyst malformations compared to control morpholinos. Cloaca malformations were also significantly increased, but to a lesser extent. The numbers below the graphs depict each group size. (C) Depletion of cry1a with SBM in the nphp8^sa24730 in-cross (F2 generation) more than doubled the frequency of glomerular cyst formation in comparison with control siblings; depletion with cry1a TBM led to a slight, but not significant increase in glomerular cysts (left graph). Depletion of cry5 with SBM or TBM in the nphp8^sa24730 in-cross (F2 generation) almost doubled the frequency of glomerular cyst formation without reaching significance (defined by P < 0.05). Glomerular cysts were expressed as fold change in relationship to control MO-injected zebrafish embryos. The numbers above the graphs depict the group size. All P-values were calculated using Fisher’s exact test.