ArticleDevelopment (Cambridge, England)2013
Dose-dependent roles for canonical Wnt signalling in de novo crypt formation and cell cycle properties of the colonic epithelium.
Article in Development (Cambridge, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Wnt signaling and tumors (Review).Molecular and clinical oncology · 2024Review
- A Wnt10a-Notch signaling axis controls Hertwig's epithelial root sheath cell behaviors during root furcation patterning.International journal of oral science · 2024Article
- C-X-C domain ligand 14-mediated stromal cell-macrophage interaction as a therapeutic target for hand dermal fibrosis.Communications biology · 2023Article
- Refined fiber inulin promotes inflammation-associated colon tumorigenesis by modulating microbial succinate production.Cancer reports (Hoboken, N.J.) · 2023Article
- Basal Cell-derived WNT7A Promotes Fibrogenesis at the Fibrotic Niche in Idiopathic Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2023Article
- Molecular regulation after mucosal injury and regeneration in ulcerative colitis.Frontiers in molecular biosciences · 2022Review
- Regulation of Limbal Epithelial Stem Cells: Importance of the Niche.International journal of molecular sciences · 2021Review
- Article
- Wnt/β-catenin signalling is dispensable for adult neural stem cell homeostasis and activation.Development (Cambridge, England) · 2021Article
- Notch signaling drives development of Barrett's metaplasia from Dclk1-positive epithelial tuft cells in the murine gastric mucosa.Scientific reports · 2021Article
- Role of adenomatous polyposis coli in proliferation and differentiation of colon epithelial cells in organoid culture.Scientific reports · 2021Article
- Article
- Cancer Stem Cells,Cells · 2020Review
- Temporal and region-specific effects of sleep fragmentation on gut microbiota and intestinal morphology in Sprague Dawley rats.Gut microbes · 2020Article
- Modelling the effect of subcellular mutations on the migration of cells in the colorectal crypt.BMC bioinformatics · 2020Article
- Stem cells in homeostasis and cancer of the gut.Molecular cancer · 2019Review
- Atoh1The EMBO journal · 2019Article
- Disparate levels of beta-catenin activity determine nephron progenitor cell fate.Developmental biology · 2018Article
- Innate Recognition of the Microbiota by TLR1 Promotes Epithelial Homeostasis and Prevents Chronic Inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Lgr5The Journal of cell biology · 2018Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
There is a gradient of β-catenin expression along the colonic crypt axis with the highest levels at the crypt bottom. In addition, colorectal cancers show a heterogeneous subcellular pattern of β-catenin accumulation. However, it remains unclear whether different levels of Wnt signalling exert distinct roles in the colonic epithelium. Here, we investigated the dose-dependent effect of canonical Wnt activation on colonic epithelial differentiation by controlling the expression levels of stabilised β-catenin using a doxycycline-inducible transgenic system in mice. We show that elevated levels of Wnt signalling induce the amplification of Lgr5+ cells, which is accompanied by crypt fission and a reduction in cell proliferation among progenitor cells. By contrast, lower levels of β-catenin induction enhance cell proliferation rates of epithelial progenitors without affecting crypt fission rates. Notably, slow-cycling cells produced by β-catenin activation exhibit activation of Notch signalling. Consistent with the interpretation that the combination of Notch and Wnt signalling maintains crypt cells in a low proliferative state, the treatment of β-catenin-expressing mice with a Notch inhibitor turned such slow-cycling cells into actively proliferating cells. Our results indicate that the activation of the canonical Wnt signalling pathway is sufficient for de novo crypt formation, and suggest that different levels of canonical Wnt activations, in cooperation with Notch signalling, establish a hierarchy of slower-cycling stem cells and faster-cycling progenitor cells characteristic for the colonic epithelium.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.