FoxO1 is essential for allantois and cardiovascular morphogenesis. (A) Morphological appearances of FoxO1-WT (+/+) and -null (−/−) embryos isolated at the indicated developmental stages. Note that null embryos died at E10.5 and manifested pericardial edema (red asterisk) and hemorrhage (yellow arrow) at E9.5 and E10.5. White arrowheads denote the allantois of E8.0 and E9.0 embryos. Note the swollen/hydropic allantois in FoxO1-null embryos at E9.0. (B) Hematoxylin and eosin (H&E) staining of transverse sections of E8.0–E10.5 embryos revealed normal cardiovascular development in FoxO1-null embryos isolated between E8.0 and E9.0 of development, whereas FoxO1-null embryos at E9.5 manifested cardiovascular malformations, including a looping defect, aberrant attachment of endocardial endothelium, and ruptured vessels (red arrowheads). DA, dorsal aorta; PHV, primary head vein; EC, endocardium; MC, myocardium; NT, neural tube.