Hypoplastic endocardial cushions in embryos lacking endothelial survivin. Transverse histologic sections of survivin^lox/lox (A,C,E,G,I,K) and tie1-cre/survivin^lox/lox (B,D,F,H,J,L) embryos were examined at E9.5 to E13.0. Both wild-type and mutant E9.5 embryos exhibit the start of cardiac neural crest colonization of the OFT (arrows in A-B). Embryos lacking endothelial cell survivin exhibit reduced E9.5 AV EMT (arrow in panel D) that subsequently results in sparsely seeded, undersized AV cushions that are detached from the adjacent myocardium (F,J). Note the few enlarged endocardial cushion mesenchymal cells in hypoplastic E11.5 mutant AV cushions (arrows in panel F). Endocardial-EMT in the OFT is also affected and results in hypoplastic conal cushions (F,H). The E13 tie1-cre/survivin^lox/lox OFT mesenchymal septum is undersized and misaligned, and exhibits double outflow right ventricle (DORV), as both the future pulmonary trunk and aorta exit the right ventricle (indicated by 2 stars in panel H), instead of the aorta exiting the left ventricle and the pulmonary trunk exiting the right ventricle (indicated by 1 star in panel G). The survivin-deficient endothelium overlying the E13 cardiomyocytes and endocardial cushions is abnormal, as there are fewer endothelial nuclei and many of the remaining nuclei are grossly enlarged (arrows in panel L). a indicates common atria; AAo, aortic arch; as, aortic sac; con, conal OFT cushions; t, truncal OFT cushions; ra, right atria, rv, right ventricle; and v, common ventricle.