Calcium is a ubiquitous and versatile second messenger that plays a central role in the development and function of a wide range of cell types, tissues and organs. Despite significant recent progress in the understanding of calcium (Ca2+) signalling in organs such as the developing and adult brain, we have relatively little knowledge of the contribution of Ca2+ to the development of tubes, structures widely present in multicellular organisms. Here we image Ca2+ dynamics in the developing notochord of Ciona intestinalis. We show that notochord cells exhibit distinct Ca2+ dynamics during specific morphogenetic events such as cell intercalation, cell elongation and tubulogenesis. We used an optogenetically controlled Ca2+ actuator to show that sequestration of Ca2+ results in defective notochord cell intercalation, and pharmacological inhibition to reveal that stretch-activated ion channels (SACs), inositol triphosphate receptor (IP3R) signalling, Store Operated Calcium Entry (SOCE), Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and gap junctions are required for regulating notochord Ca2+ activity during tubulogenesis. Cytoskeletal rearrangements drive the cell shape changes that accompany tubulogenesis. In line with this, we show that Ca2+ signalling modulates reorganization of the cytoskeletal network across the morphogenetic events leading up to and during tubulogenesis of the notochord. We additionally demonstrate that perturbation of the actin cytoskeleton drastically remodels Ca2+ dynamics, suggesting a feedback mechanism between actin dynamics and Ca2+ signalling during notochord development. This work provides a framework to quantitatively define how Ca2+ signalling regulates tubulogenesis using the notochord as model organ, a defining structure of all chordates.

中文翻译：

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在发育中的管状结构中绘制钙动力学图。

钙是一种普遍存在且用途广泛的第二信使，在多种细胞类型，组织和器官的发育和功能中起着核心作用。尽管最近在了解器官（例如发育中的大脑和成年大脑）中的钙（Ca2 +）信号传导方面取得了重大进展，但我们对Ca2 +对广泛存在于多细胞生物中的管，结构的发育的贡献的了解相对较少。在这里，我们成像了Ciona intestinalis的脊索中Ca2 +动力学。我们显示，在特定的形态发生事件，例如细胞插层，细胞伸长和微管发生过程中，脊索细胞表现出独特的Ca2 +动态。我们使用了光遗传学控制的Ca2 +促动器，证明Ca2 +的螯合会导致缺缺的脊索细胞插层，和药理学抑制作用，揭示了调节激活线粒体Ca2 +所需的伸展激活离子通道（SAC），肌醇三磷酸受体（IP3R）信号，贮藏钙离子进入（SOCE），Sarco /内质网Ca2 + -ATPase（SERCA）和间隙连接肾小管生成过程中的活动。细胞骨架重排驱动伴随肾小管生成的细胞形状变化。与此相符，我们表明，Ca2 +信号传导可调控导致脊索微管发生的形态发生事件中细胞骨架网络的重组。我们还证明，肌动蛋白细胞骨架的扰动会急剧地重塑Ca2 +动力学，提示在脊索发育过程中肌动蛋白动力学与Ca2 +信号传导之间存在反馈机制。