Role of Ca2+ transients at the node of the mouse embryo in breaking of left-right symmetry
Role of Ca2+ transients at the node of the mouse embryo in breaking of left-right symmetry
复制标题
DOI：
10.1126/sciadv.aba1195
复制
发表时间：
2020-07-01
期刊：
影响因子：
13.6
通讯作者：
Hamada, Hiroshi
中科院分区：
文献类型：
--
作者：
Mizuno, Katsutoshi;Shiozawa, Kei;Hamada, Hiroshi
不动的纤毛感知细胞外信号，例如液体流动，但 Ca2+ 是否在流动传感中发挥作用尚不清楚。在这里，我们研究了纤毛 Ca2+ 在血流传感中的作用，该血流传感启动了小鼠胚胎中左右 (L-R) 对称性的破坏。在节点的冠细胞中检测到纤毛内和细胞质 Ca2+ 瞬变。这些 Ca2+ 瞬变表现出 L-R 不对称性，这种不对称性在没有液体流动或 PKD2 通道的情况下消失。进一步的表征允许将 Ca2+ 瞬变分为两种类型：纤毛衍生的 L-R 不对称瞬变（类型 1）和不具有 L-R 偏差的纤毛独立瞬变（类型 2）。 1 型纤毛内瞬变优先发生在结节的左后区域，此处发生 L-R 对称性破缺。抑制纤毛内 Ca2+ 瞬变延迟了 L-R 对称性破缺。我们的结果表明冠细胞中纤毛衍生的 Ca2+ 瞬变参与了小鼠胚胎中 L-R 对称性破坏的启动。
Immotile cilia sense extracellular signals such as fluid flow, but whether Ca2+ plays a role in flow sensing has been unclear. Here, we examined the role of ciliary Ca2+ in the flow sensing that initiates the breaking of left-right (L-R) symmetry in the mouse embryo. Intraciliary and cytoplasmic Ca2+ transients were detected in the crown cells at the node. These Ca2+ transients showed L-R asymmetry, which was lost in the absence of fluid flow or the PKD2 channel. Further characterization allowed classification of the Ca2+ 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 Ca2+ transients delayed L-R symmetry breaking. Our results implicate cilium-derived Ca2+ transients in crown cells in initiation of L-R symmetry breaking in the mouse embryo.