The breaking of bilateral symmetry in most vertebrates is critically dependent upon the motile cilia of
the embryonic left-right organizer (LRO), which generate a directional fluid flow; however, it remains
unclear how this flow is sensed. Here, we demonstrated that immotile LRO cilia are mechanosensors for
shear force using a methodological pipeline that combines optical tweezers, light sheet microscopy, and
deep learning to permit in vivo analyses in zebrafish. Mechanical manipulation of immotile LRO cilia
activated intraciliary calcium transients that required the cation channel Polycystin-2. Furthermore,
mechanical force applied to LRO cilia was sufficient to rescue and reverse cardiac situs in zebrafish that lack
motile cilia. Thus, LRO cilia are mechanosensitive cellular levers that convert biomechanical forces into
calcium signals to instruct left-right asymmetry.
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