Myelination depends on oligodendrocyte lineage cells (OLCs) accurately sensing and responding to physical cues within the central nervous system. This work identifies the mechanosensitive ion channels PIEZO1 and PIEZO2 as key regulators of oligodendrocyte development and myelin formation. Oligodendrocyte progenitor cells detect subtle membrane displacements through PIEZO-mediated mechanosensitivity. In zebrafish, disruption of piezo1 and/or piezo2 in oligodendrocytes reduces sheath formation, myelin growth, and overall myelin output, with combined loss producing the most severe defects. These findings demonstrate that Piezo channels are critical for coordinating myelin sheath formation, expansion, and remodeling in vivo.
