Molecular Determinants of Liver Zonation
Abstract
The phenomenon of "liver zonation" is a remarkable process by which the liver fulfills its metabolic functions, involving highly dynamic transcriptional mechanisms. Its understanding is therefore a challenging issue. Zonation is reflected in heterogeneity of hepatocytes along the porto-central axis of the liver: periportal hepatocytes, located in the vicinity of the afferent portal vein, do not express the same metabolic enzymes than pericentral hepatocytes located near the efferent central vein. This is mainly dictated at the transcriptional level by specific pericentral versus periportal genetic programs. The mechanisms by which zonation is established have been extensively investigated since its initial discovery 40 years ago. The discovery in 2006 that Wnt/β-catenin pericentral signaling was a master regulator of this complex liver topology has been a major breakthrough. A major current priority in the field is the integration of the β-catenin pathway with other determinants that govern zonation of the liver.
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High Wnt concentration leads to b-catenin stabilization, Tcf7l1 degradation, and Tcf7l2 activation, resulting in activation of the pericentral gene program that includes Tbx3.
“High Wnt concentration leads to b-catenin stabilization71, Tcf7l1 degradation, and Tcf7l2 activation, resulting in the activation of the pericentral gene program, that includes Tbx3.”
From Enhancer grammar of liver cell types and hepatocyte zonation states (2022) · cites this paper as [71]
Cites
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Spatial sorting enables comprehensive characterization of liver zonation
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Spatial sorting enables comprehensive characterization of liver zonation
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Temporal analyses of postnatal liver development and maturation by single-cell transcriptomics
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Enhancer grammar of liver cell types and hepatocyte zonation states
González-Blas, C. B., Matetovici, I., Hillen, H., Taskiran, I. I., Vandepoel, R., Christiaens, V., Sansores-García, L., Verboven, E., Hulselmans, G., Poovathingal, S., et al. (2022) · doi:10.1101/2022.12.08.519575 · Cited by 5 · see citing works
- Authors
- Torre, C., Perret, C., & Colnot, S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Venue
- Progress in Molecular Biology and Translational Science
- Publisher
- Elsevier
- Published
- 2010
- Volume
- 97
- Pages
- 127-150
- ISSN
- 1877-1173 (ISSN-L)
- OpenAlex
- W1508475810
- Cited by
- 97
- References
- 4
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 17 · 2018: 7 · 2017: 5 · 2016: 10 · 2015: 6 · 2014: 11 · 2013: 3 · 2012: 6
- FWCI
- 17.83
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Progress in molecular biology and translational science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agence Nationale de la Recherche
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- liver zonation, hepatocyte heterogeneity, Wnt/β-catenin signaling, transcriptional regulation, hepatic metabolism, hepatic gene expression
- MeSH terms
- Animals, Humans, Liver, Transcription, Genetic, Signal Transduction, Body Patterning, Wnt Proteins, beta Catenin
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