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

First Author  Burke ZD Year  2018
Journal  Sci Rep Volume  8
Issue  1 Pages  2735
PubMed ID  29426940 Mgi Jnum  J:262663
Mgi Id  MGI:6163265 Doi  10.1038/s41598-018-20888-y
Citation  Burke ZD, et al. (2018) Spatiotemporal regulation of liver development by the Wnt/beta-catenin pathway. Sci Rep 8(1):2735
abstractText  While the Wnt/beta-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/beta-catenin pathway in the development of zonation in embryonic mouse liver by conditional deletion of Apc and beta-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 beta-catenin coincides with the restriction of GS expression to the terminal perivenous hepatocytes. Conditional loss of Apc resulted in the expression of nuclear beta-catenin throughout the developing liver and increased number of cells expressing GS. Conversely, conditional loss of beta-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.
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