Role of Ca(2+) transients at the node of the mouse embryo in breaking of left-right symmetry

Immotile cilia sense extracellular signals such as fluid flow, but whether Ca(2+) plays a role in flow sensing has been unclear. Here, we examined the role of ciliary Ca(2+) in the flow sensing that initiates the breaking of left-right (L-R) symmetry in the mouse embryo. Intraciliary and cytoplasmic Ca(2+) transients were detected in the crown cells at the node. These Ca(2+) transients showed L-R asymmetry, which was lost in the absence of fluid flow or the PKD2 channel. Further characterization allowed classification of the Ca(2+) transients into two types: cilium-derived, L-R-asymmetric transients (type 1) and cilium-independent transients without an L-R bias (type 2). Type 1 intraciliary transients occurred preferentially at the left posterior region of the node, where L-R symmetry breaking takes place. Suppression of intraciliary Ca(2+) transients delayed L-R symmetry breaking. Our results implicate cilium-derived Ca(2+) transients in crown cells in initiation of L-R symmetry breaking in the mouse embryo.