Fig. 3. Aberrant cardiac morphology, apoptosis, and proliferation in Isl1Cre/+;Bmpr1a mutants. (A-R) Whole mount and section analysis of cardiac morphology. Isl1Cre/+ mutants exhibited abnormal looping of the outflow tract at E9.5 (A-C,J-L), thinning of the ventricular wall by E11.5 (D-F,M-O), and outflow tract, ventricular, and atrial septal defects by E13.5 (G-I,P-R). (S-V,Z-C',G') Analysis of apoptosis. Staining with antibody to activated caspase-3 revealed less cell death in the outflow tract cushions and increased cell death in the ventricular septum in Isl1Cre/+:Bmpr1a mutants relative to wild-type littermates. Arrows in T,V,A' and C' indicate apoptotic cells. ^*P<0.05. (W-Y,D'-F',H') Analysis of cell proliferation. Staining with antibody to phosphorylated histone H3 (PHH3) demonstrated decreased proliferation in ventricular myocardium, including the septum in Isl1Cre/+;Bmpr1a mutants relative to wild-type control littermates. Arrows in X,Y,E' and F' indicate proliferating cells. ^*P<0.05. OFT, outflow tract; RV, right ventricle; LA, left atrium; RA, right atrium; AO, aorta; VS, ventricular septum; AS, atrial septum; PTA, persistent truncus arteriosus; OC, outflow tract cushions; VV, valve; -Cre, control embryos; +Cre, mutant embryos. Arrows in F and O, indicate the ventricular wall.