Liver Zonation Occurs Through a β-Catenin–Dependent, c-Myc–Independent Mechanism

Burke, Z., Reed, K., Phesse, T., Sansom, O. , Clarke, A. and Tosh, D. (2009) Liver Zonation Occurs Through a β-Catenin–Dependent, c-Myc–Independent Mechanism. Gastroenterology, 136(7), pp. 2316-2324. (doi: 10.1053/j.gastro.2009.02.063)

Abstract

Background and Aims: The Writ pathway has previously been shown to play a role in hepatic zonation. Herein, we have explored the role of 3 key components (Apc, beta-catenin, and c-Myc) of the Writ pathway in the zonation of ammonia metabolizing enzymes. Methods: Conditional deletion of Apc, beta-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 beta-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 beta-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 beta-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 Writ 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 beta-catenin dependent.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sansom, Professor Owen
• Authors: Burke, Z., Reed, K., Phesse, T., Sansom, O., Clarke, A., and Tosh, D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Gastroenterology
• ISSN: 0016-5085