Fig. 1. Developmental abnormalities in the Rxra^–/– embryo are evident at E11.5 in the aortic sac and at E12.5 in outflow tract cushion tissue. Embryos at various times during embryogenesis were analyzed for morphological malformations of the heart. Transverse sections of E10.5 wild-type (A) and Rxra^–/– (B) hearts show that the early stages of epithelial-to-mesenchymal cell transformation in outflow tract cushion tissue occurs in a similar manner between wild type and mutant. Arrows indicate mesenchymal cells that have migrated into the cardiac jelly. (C-H) Transverse sections of E11.5 embryonic hearts. Note throughout the outflow tract (OFT), the extent of mesenchymal seeding in the cushions is similar in the wild type (C,E,G) and Rxra^–/– (D,F,H). However, at this age, the aorticopulmonary (AoP) septum in the mutant shows signs of abnormal development, such as incomplete fusion with the sinistroventralconal cushion (F, arrow). (I-L) Transverse sections of E12.5 embryonic hearts. The OFT cushions have begun to fuse in the wild type (K, arrow) while they have become noticeably hypoplastic and malformed in the Rxra^–/–. Further evidence of an eventual AoP window is also observed in the Rxra^–/– (L, arrow). dd, dextrodorsalconal cushion; sv, sinistroventralconal cushion. (M,N) Quantitation of the relative number of cells was performed by counting nuclei in serial sections 40 µm apart beginning at the most cranial aspects of the OFT cushions and continuing down to the most caudal aspects of the cushions (between broken lines, M). (N) Cells from the dextrodorsalconal cushion (DDCC in M; white bars) and sinistroventralconal cushion (SVCC in M; black bars) were counted separately. Both OFT cushions were significantly smaller in the Rxra^–/–. *P<0.05. Error bars represent the s.e.m.