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Sci Rep. 2018 Feb 9;8(1):2735. doi: 10.1038/s41598-018-20888-y.

Spatiotemporal regulation of liver development by the Wnt/β-catenin pathway.

Author information

1
Centre for Regenerative Medicine, Department of Biology & Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK. Z.D.Burke@bath.ac.uk.
2
European Cancer Stem Cell Research Institute, Hadyn Ellis Building, Cardiff University, Cardiff, CF24 4HQ, UK.
3
Centre for Regenerative Medicine, Department of Biology & Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
4
The Beatson Institute, Garscube Estate, Glasgow, G61 18D, UK.
5
Centre for Regenerative Medicine, Department of Biology & Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK. D.Tosh@bath.ac.uk.

Abstract

While the Wnt/β-catenin pathway plays a critical role in the maintenance of the zonation of ammonia metabolizing enzymes in the adult liver, the mechanisms responsible for inducing zonation in the embryo are not well understood. Herein we address the spatiotemporal role of the Wnt/β-catenin pathway in the development of zonation in embryonic mouse liver by conditional deletion of Apc and β-catenin at different stages of mouse liver development. In normal development, the ammonia metabolising enzymes carbamoylphosphate synthetase I (CPSI) and Glutamine synthetase (GS) begin to be expressed in separate hepatoblasts from E13.5 and E15.5 respectively and gradually increase in number thereafter. Restriction of GS expression occurs at E18 and becomes increasingly limited to the terminal perivenous hepatocytes postnatally. Expression of nuclear β-catenin coincides with the restriction of GS expression to the terminal perivenous hepatocytes. Conditional loss of Apc resulted in the expression of nuclear β-catenin throughout the developing liver and increased number of cells expressing GS. Conversely, conditional loss of β-catenin resulted in loss of GS expression. These data suggest that the Wnt pathway is critical to the development of zonation as well as maintaining the zonation in the adult liver.

PMID:
29426940
PMCID:
PMC5807466
DOI:
10.1038/s41598-018-20888-y
[Indexed for MEDLINE]
Free PMC Article

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