Effect of gene knockdown on the hepatic progenitor population. Knockdown of pnpla3, mapk10 or pklr using ATG-site morpholinos decreased the proportion of embryos with a small progenitor population in a statistically significant manner (A,C,E), as evidenced by in situ hybridization for hhex expression at 48 hpf (B,D,F).

Effect of gene knockdown on hepatocyte gene expression and liver size. Knockdown of 8/14 genes (pnpla3, trib1, slc2a2, mapk10, cpn1, fads2, pklr and samm50) by ATG-site morpholino injection decreased the proportion of embryos with a small liver size in a statistically significant manner (A,C,E,G,I,K,M,O), as evidenced by in situ hybridization for fabp10a expression at 72 hpf (B,D,F,H,J,L,N,P).

Impact of gene knockdown on hepatic injury after ethanol or APAP treatment. Treatment of zebrafish embryos with 2% ethanol from 96 to 128 hpf leads to fatty droplet formation in embryonic livers, as detected by whole-mount Oil Red O staining (liver outlined with black dashed line) (A). Injury induction in control and ATG-site morphant embryos resulted in no statistical difference in fatty liver incidence (B). Treatment of zebrafish embryos with 2.5 mM acetaminophen (APAP) from 48 to 96 hpf leads to small livers compared with untreated controls, as assessed by in situ hybridization for the hepatocyte marker fabp10a (C). Knockdown of pnpla3, samm50 or trib1, followed by treatment with 2.5 mM APAP, increased the proportion of small livers compared with APAP treatment alone (D). *P<0.05.