The intestinal epithelium continuously renews throughout life. Canonical Wnt signalling – a major player in this renewal – both controls intestinal epithelial proliferation and maintains intestinal stem cells. The existence of a gradient of β-catenin expression along the colonic crypt axis, with the highest β-catenin levels at the bottom where the intestinal stem cells reside, suggests that Wnt signalling might have dose-dependent roles in the colonic epithelium. On , Yasuhiro Yamada, Konrad Hochedlinger and colleagues use a β-catenin-inducible mouse model to investigate this possibility. High levels of β-catenin expression induce crypt formation but reduce cell proliferation among progenitor cells, they report, whereas lower levels have the opposite effect. Notably, Notch signalling is activated in the slow-cycling crypt cells produced by β-catenin overexpression, and treatment of β-catenin-expressing mice with a Notch inhibitor turns the slow-cycling cells into actively proliferating cells. Together, these results suggest that different levels of Wnt signalling, in cooperation with Notch signalling, control the differentiation and proliferation of the colonic epithelium.
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