Proliferation and fate choice in the liver

Identifying the factors that contribute to organ progenitor cell maintenance and differentiation is of crucial importance to developmental and disease-related research. In their study of liver development, Suzuki et al. have now identified such a factor, the transcription factor Tbx3, and investigated its functions in hepatoblast proliferation and cell fate determination (see p. 1589). The authors discovered that Tbx3 is expressed in mouse hepatoblasts (which differentiate into hepatocytes and bile duct epithelial cells) using a fluorescence flow cytometry-based technique to identify different embryonic liver cell populations, which they assayed for the expression of numerous T-box genes. Tbx3 is a known transcriptional repressor of p19^ARF, so the researchers next investigated the expression of p19^ARF in normal and Tbx3-null hepatoblasts and found that Tbx3 loss results in a p19^ARF-induced growth arrest, which pushes hepatoblasts towards a bile duct epithelial fate. These findings thus show that in hepatoblasts,p19^ARF-induced growth arrest is important for activating biliary differentiation, whereas its repression by Tbx3 promotes an alternative(hepatocytic) fate.