Control of hepatic differentiation by activin/TGFbeta signaling

During liver development, liver progenitors called hepatoblasts differentiate into hepatocytes or biliary cells. Recently, we showed that the segregation between hepatocytes and biliary cells is dependent on a gradient of Activin/TGFbeta signaling, and that Activin/TGFbeta signaling is controlled in fetal liver by transcription factors of the Onecut family. Here, we discuss candidate factors possibly involved in the formation of the Activin/TGFbeta signaling gradient, how this gradient could integrate into a network of signaling pathways modulating hepatoblast differentiation, and the implications for human liver disease and therapy.