Role of Ca<sup>2+</sup> transients at the node of the mouse embryo in breaking of left-right symmetry.

Mizuno, Katsutoshi; Shiozawa, Kei; Katoh, Takanobu A; Minegishi, Katsura; Ide, Takahiro; Ikawa, Yayoi; Nishimura, Hiromi; Takaoka, Katsuyoshi et al. · Sci Adv · 2020

basic_science · Level V

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Abstract

Immotile cilia sense extracellular signals such as fluid flow, but whether Ca<sup>2+</sup> plays a role in flow sensing has been unclear. Here, we examined the role of ciliary Ca<sup>2+</sup> in the flow sensing that initiates the breaking of left-right (L-R) symmetry in the mouse embryo. Intraciliary and cytoplasmic Ca<sup>2+</sup> transients were detected in the crown cells at the node. These Ca<sup>2+</sup> 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<sup>2+</sup> 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<sup>2+</sup> transients delayed L-R symmetry breaking. Our results implicate cilium-derived Ca<sup>2+</sup> transients in crown cells in initiation of L-R symmetry breaking in the mouse embryo.