The gallbladder excretes cytotoxic bile acids to the duodenum through the cystic duct and common bile duct system. Sox17 haploinsufficiency causes the biliary atresia-like phenotypes and hepatitis in late organogenesis mouse embryos. However, the molecular and cellular mechanisms in the Sox17-haploinsufficient gallbladder and liver in the etiology of biliary atresia remain unclear. In this study, transcriptomic analyses revealed the early onset of cholecystitis in the Sox17+/- embryos, together with the appearance of ectopic cystic duct-like epithelia in their gallbladders. The embryonic hepatitis showed positive correlations with the severities of cholecystitis in individual Sox17+/- embryos, in addition that the embryonic hepatitis could be induced by conditional deletion of Sox17 in the primordial gallbladder epithelia, but not in the fetal liver hepatoblasts. The Sox17+/- gallbladder also showed the drastic reduction in Sonic hedgehog expression, leading to aberrant smooth muscle formation and defective contraction of the fetal gallbladder. The defective gallbladder contraction positively correlated with the severity of embryonic hepatitis in Sox17+/- embryos, suggesting the potential contribution of embryonic cholecystitis and fetal gallbladder contraction in the early pathogenesis of congenital biliary atresia.
- Received November 27, 2016.
- Accepted April 12, 2017.