ArticleHepatology (Baltimore, Md.)2018
Wnt/β-catenin signaling controls intrahepatic biliary network formation in zebrafish by regulating notch activity.
Article in Hepatology (Baltimore, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Beyond the Wiring: White Matter as a Dynamic Regulator of Brain Function and Disease.Neuroscience bulletin · 2026Review
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Phosphoproteomic analysis reveals the diversity of signaling behind ErbB-inhibitor-induced phenotypes.The FEBS journal · 2025Article
- Recapitulating Liver Embryology-Lessons to Be Learned for Liver Diseases.Journal of developmental biology · 2025Review
- An animal model recapitulates human hepatic diseases associated withProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Multiple susceptibility enhancer variants increasingFrontiers in genetics · 2025Article
- Liver regeneration after injury: Mechanisms, cellular interactions and therapeutic innovations.Clinical and translational medicine · 2024Review
- Lectins As Effective Tools in the Study of the Biliary Network and the Parenchymal Architecture of the Zebrafish (Zebrafish · 2024Article
- PPARα activation promotes liver progenitor cell-mediated liver regeneration by suppressing YAP signaling in zebrafish.Scientific reports · 2023Article
- Association analysis and functional follow-up identified common variants ofFrontiers in genetics · 2023Article
- Stem Cell-based Therapy Strategy for Hepatic Fibrosis by Targeting Intrahepatic Cells.Stem cell reviews and reports · 2022Review
- Maladaptive regeneration - the reawakening of developmental pathways in NASH and fibrosis.Nature reviews. Gastroenterology & hepatology · 2021Review
- Novel Therapeutic Targets in Liver Fibrosis.Frontiers in molecular biosciences · 2021Review
- Wnt/β-catenin signalling controls bile duct regeneration by regulating differentiation of ductular reaction cells.Journal of cellular and molecular medicine · 2020Article
- Core Hippo pathway components act as a brake on Yap and Taz in the development and maintenance of the biliary network.Development (Cambridge, England) · 2020Article
- Extrahepatic cholangiocyte obstruction is mediated by decreased glutathione, Wnt and Notch signaling pathways in a toxic model of biliary atresia.Scientific reports · 2020Article
- PCAT-1: A Novel Oncogenic Long Non-Coding RNA in Human Cancers.International journal of biological sciences · 2019Review
- Hdac1 Regulates Differentiation of Bipotent Liver Progenitor Cells During Regeneration via Sox9b and Cdk8.Gastroenterology · 2019Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Malformations of the intrahepatic biliary structure cause cholestasis, a liver pathology that corresponds to poor bile flow, which leads to inflammation, fibrosis, and cirrhosis. Although the specification of biliary epithelial cells (BECs) that line the bile ducts is fairly well understood, the molecular mechanisms underlying intrahepatic biliary morphogenesis remain largely unknown. Wnt/β-catenin signaling plays multiple roles in liver biology; however, its role in intrahepatic biliary morphogenesis remains unclear. Using pharmacological and genetic tools that allow one to manipulate Wnt/β-catenin signaling, we show that in zebrafish both suppression and overactivation of Wnt/β-catenin signaling impaired intrahepatic biliary morphogenesis. Hepatocytes, but not BECs, exhibited Wnt/β-catenin activity; and the global suppression of Wnt/β-catenin signaling reduced Notch activity in BECs. Hepatocyte-specific suppression of Wnt/β-catenin signaling also reduced Notch activity in BECs, indicating a cell nonautonomous role for Wnt/β-catenin signaling in regulating hepatic Notch activity. Reducing Notch activity to the same level as that observed in Wnt-suppressed livers also impaired biliary morphogenesis. Intriguingly, expression of the Notch ligand genes jag1b and jag2b in hepatocytes was reduced in Wnt-suppressed livers and enhanced in Wnt-overactivated livers, revealing their regulation by Wnt/β-catenin signaling. Importantly, restoring Notch activity rescued the biliary defects observed in Wnt-suppressed livers.
conclusionWnt/β-catenin signaling cell nonautonomously controls Notch activity in BECs by regulating the expression of Notch ligand genes in hepatocytes, thereby regulating biliary morphogenesis. (Hepatology 2018;67:2352-2366).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.