Hepatocyte nuclear factor 4α orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver
Open accessAbstract
Epithelial formation is a central facet of organogenesis that relies on intercellular junction assembly to create functionally distinct apical and basal cell surfaces. How this process is regulated during embryonic development remains obscure. Previous studies using conditional knockout mice have shown that loss of hepatocyte nuclear factor 4alpha (HNF4alpha) blocks the epithelial transformation of the fetal liver, suggesting that HNF4alpha is a central regulator of epithelial morphogenesis. Although HNF4alpha-null hepatocytes do not express E-cadherin (also called CDH1), we show here that E-cadherin is dispensable for liver development, implying that HNF4alpha regulates additional aspects of epithelial formation. Microarray and molecular analyses reveal that HNF4alpha regulates the developmental expression of a myriad of proteins required for cell junction assembly and adhesion. Our findings define a fundamental mechanism through which generation of tissue epithelia during development is coordinated with the onset of organ function.
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HNF4A has previously been implicated in regulating tissue remodeling, which is required for normal liver formation.
“HNF4A has previously been implicated in regulating tissue remodeling, which is required for normal liver formation.”
From Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation (2014) · cites this paper as Battle et al., 2006
Ablation of HNF4A specifically in the embryonic liver causes loss of cohesive tissue architecture with disruption of cell-cell junction assembly.
“Ablation of HNF4A specifically in the embryonic liver causes loss of cohesive tissue architecture with disruption of cell-cell junction assembly (Battle et al., 2006; Parviz et al., 2003).”
From Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation (2014) · cites this paper as Battle et al., 2006
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E‐cadherin controls adherens junctions in the epidermis and the renewal of hair follicles
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Transmembrane proteins of tight junctions
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HNF4A is essential for specification of hepatic progenitors from human pluripotent stem cells
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Self-citationCanonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells
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Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation
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Liu, F., Peng, Y., Qian, H., Xiao, M. C., Ding, C. H., Zhang, X., & Xie, W. F. (2024) · Journal of Digestive Diseases · doi:10.1111/1751-2980.13272 · Cited by 5 · see citing works
- Authors
- Battle, M. A., Konopka, G., Parviz, F., Gaggl, A. L., Yang, C., Sladek, F. M., & Duncan, S. A.
- Affiliations
- Medical College of Wisconsin (US)
- *Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226-0509;
- University of California, Riverside (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-05-30
- Volume
- 103
- Issue
- 22
- Pages
- 8419-8424
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1482507
- OpenAlex
- W2059879159
- Cited by
- 246
- References
- 3
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 10 · 2022: 7 · 2021: 12 · 2020: 8 · 2019: 7 · 2018: 11 · 2017: 11 · 2016: 13 · 2015: 12 · 2014: 20 · 2013: 9 · 2012: 14
- FWCI
- 13.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Nebraska Medical Center
- University of Pennsylvania
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (F32DK067808, R01DK053892)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- HNF4α, liver development, epithelial morphogenesis, cell adhesion proteins, E-cadherin, intercellular junctions, embryonic liver, organogenesis, transcriptional regulation
- MeSH terms
- Animals, Cell Differentiation, Epithelial Cells, Female, Intercellular Junctions, Liver, Male, Mice, Transgenic, Cell Adhesion Molecules, Cadherins, Gene Expression Regulation, Developmental, Microscopy, Electron, Transmission, Mice, Hepatocyte Nuclear Factor 4
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