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 p. 66, 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.
Gut feeling about Wnt doses
Gut feeling about Wnt doses. Development 1 January 2013; 140 (1): e101. doi:
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