Liver zonation occurs through a β-catenin–dependent, c-Myc–independent mechanism

Burke, Zoé D., Reed, Karen Ruth ORCID: https://orcid.org/0000-0002-7467-1718, Phesse, Toby ORCID: https://orcid.org/0000-0001-9568-4916, Sansom, Owen J. ORCID: https://orcid.org/0000-0001-9540-3010, Clarke, Alan Richard ORCID: https://orcid.org/0000-0002-4281-426X and Tosh, David 2009. Liver zonation occurs through a β-catenin–dependent, c-Myc–independent mechanism. Gastroenterology 136 (7) , pp. 2316-2324. 10.1053/j.gastro.2009.02.063

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Abstract

Background and Aims. The Wnt pathway has previously been shown to play a role in hepatic zonation. Herein, we have explored the role of 3 key components (Apc, β-catenin, and c-Myc) of the Wnt pathway in the zonation of ammonia metabolizing enzymes. Methods. Conditional deletion of Apc, β-catenin, and c-Myc was induced in the livers of mice and the expression of periportal and perivenous hepatocyte markers was determined by polymerase chain reaction, Western blotting, and immunohistochemical techniques. Results. Under normal circumstances, the urea cycle enzyme carbamoylphosphate synthetase I (CPS I) is present in the periportal, intermediate, and the first few layers of the perivenous zone. In contrast, glutamine synthetase (GS)—and nuclear β-catenin—is expressed in a complementary fashion in the last 1–2 cell layers of the perivenous zone. Conditional loss of Apc resulted in the expression of nuclear β-catenin and GS in most hepatocytes irrespective of zone. Induction of GS in hepatocytes outside the normal perivenous zone was accompanied by a reduction in the expression of CPS I. Deletion of β-catenin induces a loss of GS and a complementary increase in expression of CPS I irrespective of whether Apc is present. Remarkably, deletion of c-Myc did not perturb the pattern of zonation. Conclusions. It has been shown that the Wnt pathway is key to imposing the pattern of zonation within the liver. Herein we have addressed the relevance of 3 major Wnt pathway components and show critically that the zonation is c-Myc independent but β-catenin dependent.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology
Publisher:	Elsevier
ISSN:	0016-5085
Last Modified:	06 Jan 2023 02:07
URI:	https://orca.cardiff.ac.uk/id/eprint/9006

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