Fig. 7. jagged 2 and jagged 3 regulate development of the zebrafish intrahepatic biliary system. (A-I) Confocal projections through the liver of 5-dpf zebrafish larvae processed for cytokeratin IHC. Intrahepatic biliary development is normal in jagged 1 (B), jagged 3 (E), jagged 1/2 (F) and jagged 1/3 (not shown) morphants, when compared to wild type (A). Biliary development is abnormal in jagged 2 morphants. In low-dose jagged 2 morphants (C), rosettes of liver cells with apical cytokeratin staining are noted (arrow). High-dose jagged 2 morphants (D) have frequent rosettes (arrow) and a small complement of normal bile ducts. Co-injection of the jagged 3 morpholino with either a low dose (G), or high doses (not shown), of the jagged 2 morpholino severely disrupts intrahepatic bile duct development. These larvae have few recognizable bile ducts. Instead, immunoreactive cytokeratin is located apically, within hepatocyte rosettes (arrow), or along vascular sinusoids (asterisk) that in teleosts normally express low levels of cytokeratins. (H) Twenty percent of larvae co-injected with full-length human Jagged 1 mRNA and jagged 2/3 morpholinos have only rare rosettes (arrow). (I) Low-power confocal projection showing normal gallbladder and extrahepatic bile duct development in a jagged 2/3 morphant larva. Arrow indicates liver cell rosette; arrowhead indicates origin of common hepatic duct (chd) within the liver. cbd, common bile duct; cd, cystic duct; chd, common hepatic duct; g, gallbladder; i, intestine; l, liver; pa, pancreas; pd, pancreatic duct.