TY - JOUR
T1 - The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals
AU - Wu, Nan
AU - Nguyen, Quy
AU - Wan, Ying
AU - Zhou, Tiaohao
AU - Venter, Julie
AU - Frampton, Gabriel A.
AU - Demorrow, Sharon
AU - Pan, Duojia
AU - Meng, Fanyin
AU - Glaser, Shannon
AU - Alpini, Gianfranco
AU - Bai, Haibo
N1 - Publisher Copyright:
© 2017 USCAP, Inc All rights reserved.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development.
AB - The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development.
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U2 - 10.1038/labinvest.2017.29
DO - 10.1038/labinvest.2017.29
M3 - Article
C2 - 28581486
AN - SCOPUS:85021823912
SN - 0023-6837
VL - 97
SP - 843
EP - 853
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 7
ER -