LATS-YAP/TAZ controls lineage specification by regulating TGFβ signaling and Hnf4α expression during liver development

• DOI: 10.1038/ncomms11961
• Publication Date: 2016-06-30T09:11:58Z
• Authors: Da-Hye Lee; Jae Oh Park; Tae-Shin Kim; Sang-Kyum Kim; Tack-hoon Kim; Min-chul Kim; Gun Soo Park; Jeong-Hwan Kim; Shinji Kuninaka; Eric N. Olson; Hideyuki Saya; Seon-Young Kim; Ho Lee; Dae-Sik Lim
• Keywords: Hippo signaling pathway; Cell fate determination

Abstract The Hippo pathway regulates the self-renewal and differentiation of various adult stem cells, but its role in cell fate determination during liver development remains unclear. Here we report that controls lineage specification proliferation separately from Notch signalling, using mice primary hepatoblasts with liver-specific knockout Lats1 Lats2 kinase, direct upstream regulators YAP TAZ. During after development, activation YAP/TAZ induced by loss Lats1/2 forces or hepatocytes to commit biliary epithelial (BEC) lineage. It increases BEC fibroblast up-regulating TGFβ suppresses hepatoblast hepatocyte repressing Hnf4α expression. Notably, oncogenic induces massive p53-dependent senescence/death. Together, our results reveal activity levels govern a context-dependent manner.