Fig. 6.

Colonic regeneration required Wnts from epithelial and distinct stromal compartments. (A) Experimental scheme showing 7 days of 2.5% DSS treatment and 7 days of recovery by administering regular drinking water. Representative colon photographs at the end of the experiment (day 14) showed a reduced colon length and small cecum in Gpr177^L/L;Vil-Cre;Tagln-Cre mice. (B) Body weight analysis of mice of various genotypes, with indicated numbers, showed increased morbidity when either epithelial or stromal Wnts were blocked. Gpr177^L/L;Vil-Cre;Tagln-Cre mice (purple line) exhibited the worst disease activities with minimal body-weight recovery. Controls included Gpr177 flox/flox (no cre) littermates, as well as Vil-Cre-only mice, and tamoxifen-injected wild-type and Vil-CreER mice (non-littermates). Also see Fig. S5A. (C) No mortality was observed for wild-type mice during the experiment, whereas increased lethality was found for Gpr177^L/L;Vil-Cre;Tagln-Cre (purple line) and Gpr177^L/L;Vil-Cre;Acta2-CreER mice (blue line). Controls included Gpr177 flox/flox (no cre) littermates, as well as Vil-Cre-only mice, and tamoxifen-injected wild-type and Vil-CreER mice (non-littermates). Also see Fig. S5A. (D) Representative colon histology images of day 11 and day 14 mice following DSS treatment. Red brackets indicate regions of epithelial ulceration. (E) Scoring of mucosal damage showed increased disease indexes in Gpr177^L/L;Vil-Cre and Gpr177^L/L;Vil-Cre;Tagln-Cre mice. (F) Alcian Blue staining showed a reduction of goblet cell differentiation in recovering colons of Gpr177^L/L;Vil-Cre and Gpr177^L/L;Vil-Cre;Tagln-Cre mice. (G) Microscopic measurement of the lengths of ulceration, at day 11 and 14, showed an advancement of the pathologies in Gpr177^L/L;Vil-Cre and Gpr177^L/L;Vil-Cre;Tagln-Cre mice. Gpr177^L/L;Vil-Cre;Tagln-Cre colons had the largest epithelial wounds. (H,I) Histology and colitis-scoring of mouse colons at day 14 of experiments showed worse colitis in Gpr177^L/L;Acta2-CreER and Gpr177^L/L;Vil-CreER mice, whereas the worst disease index was in Gpr177^L/L;Vil-Cre;Acta2-CreER mice. Data are mean±s.e.m. from at least three independent experiments. ***P<0.001. Also see Fig. S5.