Figure 4.

Yolk sac and placental defects in mutant embryos. (A–D) Morphology of embryos in their yolk sacs at E9.5. Large vitelline blood vessels (arrowheads) are observed in the Notch1^+/− and Notch4^−/− yolk sacs, but not in the Notch1^−/− and Notch1^−/− Notch4^−/− mutants. (E–G) PECAM-1-stained yolk sacs. The yolk sacs of the Notch1^−/− and Notch1^−/− Notch4^−/− mutant embryos are at the primitive vascular plexus stage and have not undergone vascular remodeling to form the large and small blood vessels of the mature yolk sac. (H,I) Histological sections of PECAM-1-stained yolk sacs. The Notch1^+/− yolk sac (H) has differentiated both small capillaries (arrowheads) and large vitelline collecting vessels (arrow). The Notch1^−/− yolk sac (I) exhibits a disorganized, confluent vascular plexus. (J,K) Histological sections of placentas at E9.5. In the Notch1^+/− Notch4^−/− control embryo (J), embryonic blood vessels containing nucleated erythrocytes (arrowheads) have invaded the labyrinthine layer of the placenta. In the Notch1^−/− Notch4^−/− mutant embryo (K), embryonic blood vessels are present at the edge of the placenta but have not invaded the labyrinthine layer.