Proposed mechanotransduction pathway regulating valve delamination.
At 65 hpf, just prior to delamination, WSS (orange arrow) activates Nfatc signaling in luminal cells. This leads to the production of a secreted signal that results in the inhibition of twist1b expression in abluminal cells. Since twist1b causes abluminal cells to transition toward more mesenchymal cell states, its inhibition is necessary to allow MEndoT, a process key to correct valve delamination. EndoMT, endothelial–mesenchymal transition; hpf, hours postfertilization; MEndoT, mesenchymal–endothelial transition; WSS, wall shear stress.