Cilia function as calcium-mediated mechanosensors that instruct left-right asymmetry

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.

Automated summary

The breaking of bilateral symmetry in most vertebrates relies on the motile cilia of the embryonic left-right organizer (LRO), which generate fluid flow. This study demonstrated that the immotile LRO cilia serve as mechanosensors for shear force in zebrafish. Mechanical force applied to immotile LRO cilia activated intraciliary calcium transients, requiring the cation channel Polycystin-2. The study also showed that mechanical force applied to LRO cilia could rescue and reverse cardiac situs in zebrafish lacking motile cilia.