Fig. 7. Model describing the role of EPHs and ephrins in patterning chemokine-induced cytotrophoblast invasion. (A) A rapid switch in EPH and ephrin expression generates repulsive signals that orient cytotrophoblast (CTB) invasion away from the placenta and towards the uterine wall. (B) Within the uterine stroma, invasive cytotrophoblasts distinguish veins from arterioles based on their expression of EPHB4 and ephrin B2, respectively. Our data suggest that cytotrophoblast interactions with EPHB4-expressing cells inhibit their chemokine-induced migration, one mechanism that could restrict their remodeling of veins. By contrast, interactions with ephrin B2-expressing cells permit migration. As a result, cytotrophoblast remodeling of the uterine vasculature is biased toward the arterial side of the circulation.