Figure 3.

Altered proliferation, migration, and apoptosis in the absence of Apc. (a–f) BrdU staining in control and Apc-deficient intestinal epithelium. (a) BrdU-positivite cells in wild-type-induced Cre⁺Apc^+/+ crypts 2 h following BrdU injection are confined to a proliferative zone within the crypt. (b) The position of BrdU-positive cells in crypt–villus axis of control, induced Cre⁺Apc^+/+ mice 24 h after BrdU injection, indicating migration of labeled cells onto the villus. (c) BrdU staining in induced Cre⁺Apc^fl/fl epithelium 2 h after BrdU injection show that positively stained cells are present throughout the entire aberrant crypt-like structure. (d) BrdU staining 24 h after injection of BrdU in induced Cre⁺Apc^fl/fl intestinal epithelium. (e) Position of BrdU-positive cells within the control crypt–villus axis at 2 h (black bars) and 24 h (open bars). Position 0 represents the base of the crypt. Note the increase in position at 24 h, reflecting migration. (f) Position of BrdU cells within the crypt-like structure in induced Cre⁺Apc^fl/fl mice at 2 h (black bars) and 24 h (open bars). Unlike in the controls, no migration of labeled cells is evident. (g,h) Increased apoptosis in Apc mutant crypts. Immunohistochemical staining of active caspase 3 in induced Cre⁺Apc^+/+ mice (g) and induced Cre⁺Apc^fl/fl mutant crypts (h). This staining confirmed apoptosis counts from H&E-stained sections that showed significantly increased apoptosis in Apc deficient crypts (11.1% ± 1.2%) compared with control crypts (3.5% ± 0.45%; p = 0.01; Mann Whitney, n = 5).