ArticleHepatology (Baltimore, Md.)2008
Beta-catenin deletion in hepatoblasts disrupts hepatic morphogenesis and survival during mouse development.
Article in Hepatology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 197 citations in OpenAlex.
- Engineered microtissue systems for identifying the roles of Wnt and YAP signaling in hepatoblast differentiation and organization.Materials today. Bio · 2026Article
- Wnt/β-catenin signaling in hepatocellular carcinoma: a key player in resistance to targeted and immunotherapies.Carcinogenesis · 2026Review
- Construction of liver organoid models by hepatobiliary differentiation from human induced pluripotent stem cells: state of the art, challenges and improving strategies.Stem cell research & therapy · 2026Review
- The origin of hepatocellular carcinoma depends on metabolic zonation.Science (New York, N.Y.) · 2026Article
- Wnt signalling maintains self-renewal of human hepatoblasts without blocking their differentiation.Development (Cambridge, England) · 2025Article
- An animal model recapitulates human hepatic diseases associated withProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Wnt/β-Catenin Signaling in Liver Pathobiology.Annual review of pathology · 2025Review
- A developmental biliary lineage program cooperates with Wnt activation to promote cell proliferation in hepatoblastoma.Nature communications · 2024Article
- Loss of β-catenin reveals a role for glutathione in regulating oxidative stress during cholestatic liver disease.Hepatology communications · 2024Article
- Wnt/β-catenin signaling pathway in liver biology and tumorigenesis.In vitro cellular & developmental biology. Animal · 2024Review
- Wnt/β-Catenin signaling pathway in hepatocellular carcinoma: pathogenic role and therapeutic target.Frontiers in oncology · 2024Review
- Genome-scale CRISPR screening in a single mouse liver.Cell genomics · 2022Article
- Wnt signaling in biliary development, proliferation, and fibrosis.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis.Frontiers in oncology · 2022Review
- Role and Regulation of Wnt/β-Catenin in Hepatic Perivenous Zonation and Physiological Homeostasis.The American journal of pathology · 2022Review
- Compensatory hepatic adaptation accompanies permanent absence of intrahepatic biliary network due to YAP1 loss in liver progenitors.Cell reports · 2021Article
- Review
- Maladaptive regeneration - the reawakening of developmental pathways in NASH and fibrosis.Nature reviews. Gastroenterology & hepatology · 2021Review
- Embryonic liver developmental trajectory revealed by single-cell RNA sequencing in the Foxa2Communications biology · 2020Article
- The Canonical Wnt Pathway as a Key Regulator in Liver Development, Differentiation and Homeostatic Renewal.Genes · 2020Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledBeta-catenin, the central component of the canonical Wnt pathway, plays important roles in the processes of liver regeneration, growth, and cancer. Previously, we identified temporal expression of beta-catenin during liver development. Here, we characterize the hepatic phenotype, resulting from the successful deletion of beta-catenin in the developing hepatoblasts utilizing Foxa3-cyclization recombination and floxed-beta-catenin (exons 2 through 6) transgenic mice. Beta-catenin loss in developing livers resulted in significantly underdeveloped livers after embryonic day 12 (E12) with lethality occurring at around E17 stages. Histology revealed an overall deficient hepatocyte compartment due to (1) increased cell death due to oxidative stress and apoptosis, and (2) diminished expansion secondary to decreased cyclin-D1 and impaired proliferation. Also, the remnant hepatocytes demonstrated an immature phenotype as indicated by high nuclear to cytoplasmic ratio, poor cell polarity, absent glycogen, and decreased expression of key liver-enriched transcription factors: CCAAT-enhancer binding protein-alpha and hepatocyte nuclear factor-4alpha. A paucity of primitive bile ducts was also observed. While the stem cell assays demonstrated no intrinsic defect in hematopoiesis, distorted hepatic architecture and deficient hepatocyte compartments resulted in defective endothelial cell organization leading to overall fetal pallor.
conclusionBeta-catenin regulates multiple, critical events during the process of hepatic morphogenesis, including hepatoblast maturation, expansion, and survival, making it indispensable to survival.
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Registered trials
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