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Fig. 4. Outflow tract septation defects in Tbx2^tm1Pa/Tbx2^tm1Pa homozygous mutants (–/–), 11.5-12.5 dpc. (A) Left views of a normal heterozygote (+/–) and a homozygous mutant embryo. The mutant is suffering from circulatory distress. (B,C) Ventral view of hearts from the 12.5 dpc embryos in A (B) and a normal heterozygous 11.5 dpc heart (C) for comparison. The 12.5 dpc homozygous mutant aorta (red arrowhead) is abnormally positioned to the right relative to the pulmonary trunk (yellow arrowhead). (D-I) Transverse histology of wild-type (D-F, +/+) and homozygous mutant embryos (G-I) over a range of stages between 11.5 and 12.5 dpc. Homozygous mutant histology shows delayed outflow tract (OFT) septation into separate aortic (red arrowheads) and pulmonary (yellow arrowheads) outlets. (J,K) Transverse histology from 12.5 dpc wild-type (J) and homozygous mutant embryos (K). Homozygous mutants frequently show a misalignment where the aortic outlet is abnormally positioned with respect to the left ventricle. Normally at 12.5 dpc the aortic outlet is situated near the left ventricle, separated only by endocardial cushion (blue arrowhead in J). (L) The right 6th arch artery (green arrowhead) is often persistent in 12.5 dpc homozygous mutant embryos. ra, right atrium; la, left atrium; rv, right ventricle; lv, left ventricle; as, aortic sac; e, esophagus; da, descending aorta; dar, ductus arteriosus.

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