Fig. 7. Notch and ephrin-B2/EphB4 pathways regulate the balanced anterior DA and CV morphogenesis. (A) Summary of DA and CV phenotypes at E9.0. In wild type, all ECs in the DA express ephrin B2 (red) and all ECs in the CV express EphB4 (blue). In the gain-of-function Notch mutants, the DA is enlarged whereas the CV is reduced, and cells in the CV, in addition to the DA, express ephrin B2. Some CV cells co-express ephrin B2 and EphB4 (purple striped). The ratio of arterial to venous ECs is increased. In the loss-of-function Notch mutant, the DA is reduced while the CV is enlarged, and some ECs in the DA, in addition to the CV, express EphB4. The ratio of arterial to venous ECs is reduced. In both loss-of-function Efnb2 and Ephb4 mutants, the DA is enlarged, whereas the CV is reduced. The enlarged DA bears some ECs with venous identity, ephrin B2^- and EphB4⁺ (blue). The CV size is reduced and its ECs express EphB4. (B) Proposed model depicts the Notch and ephrin B2/EphB4 pathways as molecular regulators in the balanced growth of the DA and CV. Alterations in the size of one type of vessel are accompanied by reciprocal changes in the other. Notch signaling controls this equilibrium by promoting arterial differentiation, thereby dictating the ratio of arterial to venous ECs. Ephrin B2/EphB4 signaling regulates this balance by sorting differential ECs into the respective vessels.