Fig. 3.

A proposed mechanism of Hippo-YAP/TAZ signaling pathway function in lymphatic valve (LV) formation. LVs develop in a step-wise manner. LV-ECs are specified in red and LECs are in green. Blue lines indicate VEGFR3. Briefly, during the initiation stage, OSS promotes high PROX1 and FOXC2 expression in LV-ECs. During the valve maturation stage, LV-ECs orient perpendicular to the flow and migrate into the vessel lumen. Then, LV-ECs elongate to form a bi-layered leaflet with a thick extracellular matrix (ECM). YAP/TAZ activities are gradually increased during the maturation stage, thereby indicating that Hippo YAP/TAZ signaling pathway is regulated by a multitude of signaling mechanisms for LV development.