Extrinsic control of Wnt signaling in the intestine

• Published in: Differentiation (London) Vol. 97; pp. 1 - 8
• Main Author: Koch, Stefan
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.09.2017; Elsevier Science Ltd
• Subjects: Cell Differentiation - genetics; Cell Proliferation - genetics; Cell signaling; Colitis; Colitis - complications; Colitis - genetics; Colitis - pathology; Colon; Colorectal cancer; Control; Digestive system; Digestive tract; Epithelial cells; Gene Expression Regulation - genetics; Homeostasis; Homeostasis - genetics; Humans; IBD; Inflammatory bowel diseases; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - pathology; Inflammatory diseases; Intestinal epithelial cells; Intestine; Intestines - metabolism; Intestines - pathology; Neoplasms - complications; Neoplasms - genetics; Neoplasms - pathology; Organoids; Paracrine signalling; Signal transduction; Stem cells; Stem Cells - metabolism; Stem Cells - pathology; Stromal cells; Wnt protein; Wnt Signaling Pathway - genetics; β-catenin; IL; CAC; NFκB; TCF/LEF; CBC; DKK; RSPO; Intestinal epithelial cells; Colorectal cancer; IBD; LRP; TNF; ZNRF/RNF; Cell signaling; IFN; FZD; APC; LGR; Colon; PCP; WNT; GSK
• ISSN: 0301-4681; 1432-0436; 1432-0436
• DOI: 10.1016/j.diff.2017.08.003

The canonical Wnt/β-catenin signaling pathway is a central regulator of development and tissue homeostasis. In the intestine, Wnt signaling is primarily known as the principal organizer of epithelial stem cell identity and proliferation. Within the last decade, numerous scientific breakthroughs have shed light on epithelial self-organization in the gut, and organoids are now routinely used to study stem cell biology and intestinal pathophysiology. The contribution of non-epithelial cells to Wnt signaling in the gut has received less attention. However, there is mounting evidence that stromal cells are a rich source of Wnt pathway activators and inhibitors, which can dynamically shape Wnt signaling to control epithelial proliferation and restitution. Elucidating the extent and mechanisms of paracrine Wnt signaling in the intestine has the potential to broaden our understanding of epithelial homeostasis, and may be of particular relevance for disorders such as inflammatory bowel diseases and colitis-associated cancers.