Fig. 1

Homoeostasis is unperturbed after LGK974 treatment. a C57BL/6 mice were treated with LGK974 for 4.5 days. The small intestine showed no toxicity and no difference in proliferation (BrdU). Treatment of LGK974 leads to downregulation of the intestinal stem cell genes Lgr5 and Olfm4 as confirmed by RNA in situ hybridisation. Note only a few cells at the bottom of the crypt still express Olfm4 after LGK974 treatment (N = 3 for both groups). b Quantification of BrdU+ cells/half-crypt (at least 30 crypts per mouse were analysed). Each dot represents the average per mouse, red bar = mean per group. Vehicle (VEH) N = 3, LGK974 (LGK) N = 4. c qRT-PCR confirms downregulation of several stem cell genes, whereas expression of Bmi1 is unchanged. Each dot represents single mouse sample, black bar indicates mean per group, N = 3 per group. d Uninduced Catnb^{lox(ex3)/lox(ex3)} are hypomorphs with about 50% reduced expression of β-catenin (Ctnnb1), as confirmed by qRT-PCR (N = 3). e Reduced expression of β-catenin results in hyper-sensitivity to LGK974 and loss of the (small) intestinal crypts within 10 days (mean survival), N = 8. Scale bar = 50 µm