The Significance of the Piezo1-Mediated Mechanotransduction Pathway in Normal Morphogenesis

Mechanical forces are fundamental drivers of morphogenesis, yet the molecular mechanisms that convert these physical cues into transcriptional responses remain incompletely understood. This review synthesizes current evidence identifying the mechanosensitive ion channel Piezo1 as a master regulator of developmental processes. The structural and biophysical principles underlying Piezo1 function are highlighted, focusing on its trimeric architecture and force-from-lipids gating mechanism that directly couples membrane tension to Ca 2+ influx. Its spatiotemporal expression during embryogenesis is reviewed, and the downstream pathways it activates are examined, including mitogen-activated protein kinase (MAPK) and yes-associated protein/transcriptional co-activator with PDZ-binding moti (YAP/TAZ), alongside crucial crosstalk with canonical morphogen signaling cascades such as Notch, Wntwingless/integrated signaling pathway (Wnt)/beta-catenin (β-catenin), and bone morphogenetic protein/transforming growth factor-beta (BMP/TGF-β). Functional studies across diverse model systems demonstrate that Piezo1 orchestrates conserved morphogenetic events, including vascular and lymphatic patterning, neurogenesis, epithelial morphogenesis, myoblast fusion, and osteogenesis. Human genetic data further underscore its nonredundant role, linking gain-of-function mutations to dehydrated hereditary stomatocytosis and loss-of-function mutations to primary lymphatic dysplasia. Collectively, these findings establish Piezo1 as an essential integrator of mechanical and biochemical signals, central to tissue patterning and organ formation. The review concludes by emphasizing Piezo1’s therapeutic potential in regenerative medicine and developmental disorders, while also underscoring the challenges of targeting such a broadly influential mechanosensor.