Swimming motions evoke Ca ²⁺ events in vascular endothelial cells of larval zebrafish via mechanical activation of Piezo1

Calcium signaling in blood vessels regulates their growth ^1,2 , immune response ³ , and vascular tone ⁴ . Vascular endothelial cells are known to be mechanosensitive ^5–7 , and it has been assumed that this mechanosensation mediates calcium responses to pulsatile blood flow ^8–10 . Here we show that in larval zebrafish, the dominant trigger for vascular endothelial Ca ²⁺ events comes from body motion, not heartbeat-driven blood flow. Through a series of pharmacological and mechanical perturbations, we showed that body motion is necessary and sufficient to induce endothelial Ca ²⁺ events, while neither neural activity nor blood circulation is either necessary or sufficient. Knockout and temporally restricted knockdown of piezo1 eliminated the motion-induced Ca ²⁺ events. Our results demonstrate that swimming-induced tissue motion is an important driver of endothelial Ca ²⁺ dynamics in larval zebrafish.