Wnt pathway regulation of intestinal stem cells

• Published in: The Journal of physiology Vol. 594; no. 17; pp. 4837 - 4847
• Main Authors: Mah, Amanda T., Yan, Kelley S., Kuo, Calvin J.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2016; John Wiley and Sons Inc
• Subjects: Animals; Gastrointestinal, Hepatic and Pancreatic Physiology; Homeostasis; Intestines - cytology; Intestines - physiology; Regeneration; Signalling Pathways; Special section reviews: GI stem cells ‐ new insights into roles in physiology and pathophysiology; Stem cells; Stem Cells - physiology; Symposium Review; Wnt Signaling Pathway
• ISSN: 0022-3751; 1469-7793; 1469-7793
• DOI: 10.1113/JP271754

Wnt signalling is involved in multiple aspects of embryonic development and adult tissue homeostasis, notably via controlling cellular proliferation and differentiation. Wnt signalling is subject to stringent positive and negative regulation to promote proper development and homeostasis yet avoid aberrant growth. Such multi‐layer regulation includes post‐translational modification and processing of Wnt proteins themselves, R‐spondin (Rspo) amplification of Wnt signalling, diverse receptor families, and intracellular and extracellular antagonists and destruction and transcription complexes. In the gastrointestinal tract, Wnt signalling is crucial for development and renewal of the intestinal epithelium. Intestinal stem cells (ISCs) undergo symmetric division and neutral drift dynamics to renew the intestinal epithelium. Sources of Wnts and Wnt amplifers such as R‐spondins are beginning to be elucidated as well as their functional contribution to intestinal homeostasis. In this review we focus on regulation of ISCs and intestinal homeostasis by the Wnt/Rspo pathway, the potential cellular sources of Wnt signalling regulators and highlight potential future areas of study. Wnt signalling in intestinal homeostasis. The tightly regulated Wnt signalling pathway is active at the crypt base where Wnt and Rspo signals (blue) are coming from intestinal mesenchymal and epithelial compartments. It is crucial in intestinal homeostasis by acting on crypt base columnar intestinal stem cells (green) to promote self‐renewal, yet has little effect on quiescent intestinal stem cells (red).