Comparative and immunohistochemical analyses on hepatic zonation in vertebrates with a special reference to evolution
Nobuyoshi Shiojiri1,2, Noriaki Ota3,4, Haruka Hirose5
1Graduate School of Science and Technology, Shizuoka University, Oya 836, Suruga-Ku, Shizuoka City, Shizuoka, 422-8529, Japan. shiojiri.nobuyoshi@shizuoka.ac.jp.
Cell and Tissue Research
|March 25, 2026
Summary
Hepatic zonation, crucial for liver function, is present in mammals and some fish, but not consistently across all vertebrates. Mammalian livers uniquely show pericentral glutamine synthase expression, indicating evolutionary divergence in liver zonation.
Area of Science:
- Comparative Hepatology
- Evolutionary Biology
- Biochemistry
Background:
- Liver lobules in mammals exhibit functional zonation.
- The presence and extent of hepatic zonation across vertebrate taxa remain unclear.
- Vertebrate livers present two main architectures: portal triad (non-teleosts) and non-portal triad (teleosts).
Purpose of the Study:
- To investigate hepatic zonation in diverse vertebrate species.
- To correlate hepatic zonation patterns with liver architecture and evolutionary history.
- To determine the evolutionary acquisition of hepatic zonation.
Main Methods:
- Histochemical and immunohistochemical analyses of liver tissues.
- Examination of metabolic enzymes, ammonia-metabolizing enzymes, cell adhesion molecules, and transcription factors.
- Comparative study across mammals, birds, amphibians, reptiles, and teleosts.
Main Results:
- Typical hepatic zonation of metabolic enzymes (e.g., phosphoenolpyruvate carboxykinase, Cyp1a2) observed in mammals.
- Pericentral glutamine synthase expression, an ammonia-metabolizing enzyme, is unique to mammalian species.
- Some teleosts and birds exhibit zonation for specific markers (e.g., alkaline phosphatase activity, PAS-positive substances), but not consistently for metabolic enzymes.
Conclusions:
- Hepatic zonation is not strictly linked to the two major liver architectures.
- Mammals and certain teleosts have independently evolved significant hepatic zonation.
- Pericentral glutamine synthase zonation is a distinctive mammalian trait, highlighting unique evolutionary adaptations.
