Immotile cilia of the mouse node sense a fluid flow–induced mechanical force for left-right symmetry breaking

Abstract

Immotile cilia of crown cells at the node of mouse embryos are required for sensing of a leftward fluid flow1 that gives rise to the breaking of left–right (L–R) symmetry2. The flow–sensing mechanism has long remained elusive, however, with both mechanosensing and chemosensing models having been proposed1,3–5. Here we show that immotile cilia at the mouse node respond to mechanical force. In the presence of a leftward flow, immotile cilia on the left side of the node bend toward the ventral side whereas those on the right side bend toward the dorsal side. Application of mechanical stimuli to immotile cilia along the dorsoventral axis by optical tweezers induced Ca2+ transients and degradation of Dand5 mRNA–the first known L–R asymmetric molecular events–in the targeted cells. The Pkd2 channel protein was found to be preferentially localized to the dorsal side of immotile cilia on both left and right sides of the node, and the observed induction of Ca2+ transients preferentially by mechanical stimuli directed toward the ventral side could explain the differential response of immotile cilia to the directional flow. Our results thus suggest that immotile cilia at the node sense the direction of fluid flow in a manner dependent on a flow–generated mechanical force.

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

“…Our conclusions in the zebrafish LRO utilizing CiliaSPOT mirrored results in the mouse LRO in an accompanying research article ( 48 ). Both studies independently interrogated the function of cilia as calcium-mediated mechanosensors in the LRO using different experimental models and cilia deflection approaches.…”

Quantum noise may limit the mechanosensory sensitivity of the left-right organizer of the vertebrate bodyplan

“…Exactly how cilium displacement being coupled to molecules out of equilibrium and with quantum-mechanical coherence might be achieved chemically and biologically remains to be seen, but an important theoretical point from the side of physics is that it would enable a mechanosensing mechanism to be viable. And from the position it was possible to take up until recently that the question of the sensory mechanism operating in the organizer is still an open one [4], the latest experimental results in both zebrafish [35] and mouse [36] lead one seemingly inexorably towards the conclusion that the organizer system must be using mechanosensing.…”