Notch and Wnt signals show a synergistic impact on intestinal tumorigenesis. (A–D) Small intestine (A and B) and colon (C and D) of N/Apc mice (B and D) present a high number of macroscopically visible lesions compared with control tissues (A and C). (E) Kaplan–Meier survival of N/Apc mice and their single transgenic littermates over a period of 437 days. The N/Apc compound mice (in red) are all dead by 4 months, whereas the Apc single-mutant mice (in black) start dying at ≈6 months of age, and the N mice (in green) present a normal lifespan. (F–K) Thin sections of intestinal adenomas from Apc+/− (F, H and J) and N/Apc (G, I, and K) mice. (F and G) Tissues are stained with the proliferation marker Ki67 (in red) and an antibody recognizing the villin protein (in green). (H and I) Antibody identifying β-catenin reveals cytoplasmic and nuclear localization of β-catenin in both tumors, indicative of active Wnt signaling. (J and K) Anti-GFP staining reveals the presence of the Notch-ires-GFP transgene in N/Apc tumors (K). [Scale bar, 1 cm (A–D), 50 μm (F, G, J, and K), and 25 μm (H and I).]