Chemosignalling, mechanotransduction and ciliary behaviour in the embryonic node: Computational evaluation of competing theories
Chemosignalling, mechanotransduction and ciliary behaviour in the embryonic node: Computational evaluation of competing theories
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胚胎节点的化学信号传导、机械传导和纤毛行为：竞争理论的计算评估
DOI：
10.1177/0954411914531117
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发表时间：
2014-05-01
期刊：
影响因子：
1.8
通讯作者：
Ventikos, Yiannis
中科院分区：
文献类型：
--
作者：
Chen, Duanduan;Norris, Dominic;Ventikos, Yiannis
对左右不对称的精确描述对于构建脊椎动物内部器官的模式是必不可少的。在胚胎结节内，向后极化的纤毛旋转，导致向左的流体流动(结节流动)，从而建立左右不对称。胚胎感知结节流的机制仍然不确定。现有的假说认为，要么结节流携带形态原(S)或脂质结合的囊泡向左侧，从而产生不对称信号，和/或机械感觉纤毛感知这种单向流，刺激左侧细胞内钙信号。到目前为止，还缺乏支持这些假说的直接和确凿的证据。在这项研究中，我们进行了多尺度的研究，模拟了节状纤毛和流体环境，分析了左右信号的传输。利用计算模拟技术，通过求解相关的三维非定常输运方程，研究了活性纤毛旋转产生的流态。通过在计算域中引入稀相粒子和稀相粒子，我们分别研究了形态物质和结节泡囊的输运。此外，通过扩展分析包括被动可变形纤毛的固体力学以及它们的结构行为与新兴流体力学的耦合，我们研究了被动纤毛对节流的响应。我们的结果再现了单向结节流，使我们能够评估化学和机械传感假说的合理性。对流速、分子传输和分布的定量测量为打破信号对称性所需的形态原分子量提供了指导。被动的感觉纤毛变形表明这种机械信号机制是可信的。
Precise specification of left-right asymmetry is essential for patterning the internal organs of vertebrates. Within the embryonic node, posteriorly polarised cilia rotate, causing a leftward fluid flow (nodal flow) that establishes left-right asymmetry. The mechanism by which an embryo senses nodal flow remains uncertain. Existing hypotheses argue that either nodal flow carries morphogen(s) or lipid-bounded vesicles towards the left, thereby generating an asymmetric signal, and/or that mechano-sensory cilia sense this unidirectional flow, stimulating left-sided intracellular calcium signalling. To date, direct and definitive evidence supporting these hypotheses has been lacking. In this study, we conduct a multi-scale study to simulate the nodal cilia and the fluidic environment, analysing left-right signal transmission. By employing computational simulation techniques and solving the relevant three-dimensional unsteady transport equations, we study the flow pattern produced by the rotation of active cilia. By importing dilute species and particles into the computational domain, we investigate the transport of morphogens and nodal vesicular parcels, respectively. Furthermore, by extending the analysis to include the solid mechanics of passive deformable cilia and the coupling of their structural behaviour with the emerging fluid mechanics, we study the response of passive cilia to the nodal flow. Our results reproduce the unidirectional nodal flow, allowing us to evaluate the plausibility of both chemo- and mechano-sensing hypotheses. The quantitative measurements of the flow rate, the molecular transport and distribution provide guidance regarding the necessary morphogen molecular weights to break signalling symmetry. The passive sensory ciliary deformation gives indications regarding the plausibility of this mechano-signalling mechanism.