Figure 4. Activation of canonical Wnt signaling by β-catenin stabilization increases AHF and right heart development and proliferation.

(A and B) SM22α-cre mice were crossed to Catnb^flox(ex3)/+ mice to generate SM22cre/Catnb^flox(ex3)/+ mutant embryos. SM22cre/Catnb^flox(ex3)/+ mutants had enlarged hearts, in particular the right ventricles (arrows), at E9.5. (C and D) Increased cell mass was also observed in the anterior foregut mesoderm surrounding the trachea, where a pool of Isl-1–positive AHF progenitors resides, at E10.5. (E and F) Isl-1 immunostaining was increased in the AHF (brackets) and outflow tracts (arrowheads) of SM22cre/Catnb^flox(ex3)/+ mutants at E10.5. (G) Quantitation of the increase in Isl-1 immunostaining revealed a greater than 50% increase in Catnb^flox(ex3)/+ mutants. (H–M) Isl-1 and Ki-67 double immunofluorescent staining reveal increased proliferation in Isl-1–positive cells within the outflow tracts of SM22cre/Catnb^flox(ex3)/+ mutant embryos at E10.5 (arrowheads). (N) Ki-67 staining in Isl-1–positive cells increased approximately 40% within SM22cre/Catnb^flox(ex3)/+ embryos. *P < 0.02. Scale bars: 500 μm (A and B); 75 μm (C–F); 100 μm (H–M).