The initiation of liver development is dependent on Foxa transcription factors
Abstract
The specification of the vertebrate liver is thought to occur in a two-step process, beginning with the establishment of competence within the foregut endoderm for responding to organ-specific signals, followed by the induction of liver-specific genes. On the basis of expression and in vitro studies, it has been proposed that the Foxa transcription factors establish competence by opening compacted chromatin structures within liver-specific target genes. Here we show that Foxa1 and Foxa2 (forkhead box proteins A1 and A2) are required in concert for hepatic specification in mouse. In embryos deficient for both genes in the foregut endoderm, no liver bud is evident and expression of the hepatoblast marker alpha-fetoprotein (Afp) is lost. Furthermore, Foxa1/Foxa2-deficient endoderm cultured in the presence of exogenous fibroblast growth factor 2 (FGF2) fails to initiate expression of the liver markers albumin and transthyretin. Thus, Foxa1 and Foxa2 are required for the establishment of competence within the foregut endoderm and the onset of hepatogenesis.
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Foxa2 null mice fail to form regions of definitive endoderm that give rise to liver.
“Foxa2 null mice fail to form regions of definitive endoderm that give rise to liver (Lee et al., 2005)”
From Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation (2014) · cites this paper as Lee et al., 2005
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“For example, FOXA2 is essential for both pancreas and liver development (Lee et al. 2005; Gao et al. 2008).”
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“Foxa2 null mice fail to form regions of definitive endoderm that give rise to liver (Lee et al., 2005), and conditional Foxa2 deletion in late fetal hepatocytes causes sensitivity to a cholic-acidcontaining diet, triggering a toxic accumulation of bile salts, endoplasmic reticulum stress, and liver…”
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Signalling pathways and transcriptional regulators orchestrating liver development and cancer
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- Authors
- Lee, C. S., Friedman, J. R., Fulmer, J. T., & Kaestner, K. H.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Kaestner, Klaus H.
- Venue
- Nature
- Published
- 2005-06
- Volume
- 435
- Issue
- 7044
- Pages
- 944-947
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1994942890
- Cited by
- 581
- References
- 2
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 24 · 2023: 28 · 2022: 24 · 2021: 35 · 2020: 29 · 2019: 24 · 2018: 30 · 2017: 23 · 2016: 35 · 2015: 35 · 2014: 26 · 2013: 33 · 2012: 22
- FWCI
- 9.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- FOXA1, FOXA2, forkhead transcription factor, liver development, hepatogenesis, foregut endoderm, alpha-fetoprotein, albumin, prealbumin, fibroblast growth factor 2, chromatin condensation, organogenesis, mouse embryo
- MeSH terms
- Animals, DNA-Binding Proteins, Liver, Nuclear Proteins, RNA, Messenger, Transcription Factors, Fibroblast Growth Factor 2, Gene Deletion, Gene Expression Regulation, Developmental, Mice, Hepatocyte Nuclear Factor 3-alpha, Hepatocyte Nuclear Factor 3-beta, Hepatocyte Nuclear Factor 3-gamma
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