Piezo1 and Piezo2 collectively regulate jawbone development

Piezo1 and Piezo2 are novel mechanosensory ion channels that transduce mechanical stimuli from the environment into intracellular biochemical signals in various tissues and organ systems. Here, we showed that Piezo1 and Piezo2 displayed a robust expression during jawbone development. Deletion of Piezo1 in neural crest cells caused jawbone malformations in a small but significant number of mice. We further demonstrated that disruption of Piezo1 and Piezo2 in neural crest cells caused more striking defects in jawbone development than any single knockout, suggesting essential but partially redundant roles of Piezo1 and Piezo2. In addition, we observed defects in other neural crest derivatives such as malformation of the vascular smooth muscle in double knockout mice. Moreover, TUNEL examinations revealed excessive cell death in osteogenic cells of the maxillary and mandibular arches of the double knockout mice, suggesting that Piezo1 and Piezo2 together regulate cell survival during jawbone development. We further demonstrated that Yoda1, a Piezo1 agonist, promotes mineralization in the mandibular arches. Altogether, these data firmly establish that Piezo channels play important roles in regulating jawbone formation and maintenance.