Piezo1-mediated mechanotransduction in choroid plexus epithelial cells governs ciliogenesis and cerebrospinal fluid homeostasis

Multiciliated choroid plexus epithelial cells (CPECs) are responsible for cerebrospinal fluid (CSF) production and are exposed to mechanical stimuli derived from CSF flow and intercellular contacts. However, their mechanotransduction mechanisms remain poorly understood. Here, we show that the mechanically activated ion channel Piezo1 is prominently expressed in apical and lateral membranes of mature CPECs, mediates mechanically evoked currents and CA²⁺ influx in response to both fluid flow and pharmacological activation by Yoda1, and maintains the CA²⁺ homeostasis in a cell-cell contact-dependent manner. Either knockout or overexpression of Piezo1 in CPECs led to severe hydrocephalus in mice, reduced CSF flow, disrupted ciliary maintenance, and altered expression of cilia-related genes. Piezo1-mediated CA²⁺ homeostasis regulates ciliogenesis of primary cultured CPECs. These findings establish Piezo1 as a critical mechanotransducer in CPECs for controlling the homeostasis of CA²⁺ signaling, ciliogenesis and CSF, and its mechanopathological linkage to hydrocephalus.