Abstract
The canonical Wnt (Wnt/β-catenin) signalling pathway is highly conserved and plays a critical role in regulating cellular processes both during development and in adult tissue homeostasis. The Wnt/β-catenin signalling pathway is vital for correct body patterning and is involved in fate specification of the gut tube, the primitive precursor of liver. In adults, the Wnt/β-catenin pathway is increasingly recognised as an important regulator of metabolic zonation, homeostatic renewal and regeneration in response to injury throughout the liver. Herein, we review recent developments relating to the key role of the pathway in the patterning and fate specification of the liver, in the directed differentiation of pluripotent stem cells into hepatocytes and in governing proliferation and zonation in the adult liver. We pay particular attention to recent contributions to the controversy surrounding homeostatic renewal and proliferation in response to injury. Furthermore, we discuss how crosstalk between the Wnt/β-catenin and Hedgehog (Hh) and hypoxia inducible factor (HIF) pathways works to maintain liver homeostasis. Advancing our understanding of this pathway will benefit our ability to model disease, screen drugs and generate tissue and organ replacements for regenerative medicine.
Highlights
The canonical Wnt (Wnt/β-catenin) signalling pathway is an ancient and highly conserved pathway common to all metazoans [1]
Conditional deletion of endothelial Wnt ligand secretion protein (WLS), a protein which facilitates the exocytosis of Wnt ligands, inhibits expression of glutamine synthetase (GS), CYP2E1 and Claudin2 in perivenous hepatocytes in adult mice [83]. Together these findings suggest that during development, Claudin2 does not share the tightly Wnt/β-catenin regulated expression of GS, though it does rely on Wnt/β-catenin signalling for maintenance in adulthood
We have highlighted important developments in the study of Wnt/β-catenin signalling in liver development and homeostasis
Summary
The canonical Wnt (Wnt/β-catenin) signalling pathway is an ancient and highly conserved pathway common to all metazoans [1]. The Wnt/β-catenin signalling pathways plays a central role in regulating proliferation and differentiation during development as well as in stem cell renewal [9,10]. The Wnt/β-catenin signalling pathway is involved in the formation of the primitive streak and anterior–posterior axis patterning through regulation of downstream Nodal expression. Applied in an in vitro setting, it has been shown that pre-exposure of human embryonic stem (hES) cells to Wnt/β-catenin signals is required in order for these cells to competently respond to Activin/Nodal signalling This is a pre-requisite for the homogenous formation of DE expressing the pan-endoderm markers C-X-C motif chemokine receptor 4 (CXCR4) and FOXA2 [41]. This includes activation of transcription factors, including FOXA2 and SRY-related HMG-box (SOX) 17, which are required for specification, commitment and future patterning of the DE [46,47]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
