Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration

Although Ape is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accumulation of beta-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such that Ape-deficient cells maintain a crypt progenitor-like phenotype. Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting.