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

Burke, Z. D., Reed, K. R., Yeh, S.-W., Meniel, V., Sansom, O. J. , Clarke, A. R. and Tosh, D. (2018) Spatiotemporal regulation of liver development by the Wnt/β-catenin pathway. Scientific Reports, 8, 2735. (doi: 10.1038/s41598-018-20888-y) (PMID:29426940) (PMCID:PMC5807466)

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.

• Item Type: Articles
• Additional Information: This study was supported by MRC (MR/J006793/1 to DT) and Cancer Research UK (ARC).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sansom, Professor Owen
• Authors: Burke, Z. D., Reed, K. R., Yeh, S.-W., Meniel, V., Sansom, O. J., Clarke, A. R., and Tosh, D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Scientific Reports
• Publisher: Nature Research
• ISSN: 2045-2322
• ISSN (Online): 2045-2322
• Published Online: 09 February 2018
• Copyright Holders: Copyright © The Authors 2018
• First Published: First published in Scientific Reports 8:2735
• Publisher Policy: Reproduced under a Creative Commons license