Geometry can provide long-range mechanical guidance for embryogenesis.
Geometry can provide long-range mechanical guidance for embryogenesis.
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DOI：
10.1371/journal.pcbi.1005443
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发表时间：
2017-03
影响因子：
4.3
通讯作者：
Étienne J
中科院分区：
文献类型：
--
作者：
Dicko M;Saramito P;Blanchard GB;Lye CM;Sanson B;Étienne J
在基因表达的下游，效应子如肌动球蛋白收缩机制驱动胚胎形态发生。在果蝇胚轴延伸过程中，肌动球蛋白具有特殊的平面极化组织，负责定向细胞插入。除了这些细胞重排，细胞形状的变化也有助于组织变形。虽然细胞自主动力学得到了很好的描述，但理解组织规模的行为挑战我们解决整个胚胎规模的相应机械问题，因为所有相邻上皮细胞的机械阻力将反馈到单个细胞上。在这里，我们提出了一种新的数值方法来计算全胚胎动力学的肌动球蛋白丰富的顶端上皮表面。我们在模型中输入肌动球蛋白收缩性的特定模式，例如在胚胎的腹侧区域中肌动球蛋白的平面极化。组织应变率和位移，然后预测在整个胚胎表面根据全球平衡的应力和材料的行为的上皮。上皮细胞建模使用流变学定律，涉及变形率的局部应力和肌动球蛋白各向异性收缩。预测的流动模式是一致的细胞流动时，观察到的成像果蝇轴延伸在托托，使用光片显微镜。模型和实验数据之间的协议表明，平面极化肌动球蛋白的各向异性收缩腹外侧胚带组织可以直接导致整个胚胎的组织规模的变形。三维机械平衡取决于胚胎的几何形状，其曲面在模拟中被考虑在内。重要的是，我们发现，要重现实验流量，该模型需要存在的头沟，位于前方的延伸组织的折叠。这种几何特征的存在，通过整体机械平衡，引导流动并使延伸朝向后端。生物体的形态发生是一个形成过程，在此过程中，遗传程序控制着一系列分子变化，这些变化将导致原始胚胎获得新的形状。虽然我们对遗传程序下游关键分子的时间和空间分布有了越来越多的了解，但对于这些模式如何产生适当的机械力，以便以正确的方式使组织变形，仍然存在理解上的差距。在本文中，我们展示了一个模型的组织力学可以链接到轴延伸的过程中，这是一个无处不在的发育中的动物胚胎的形态发生运动的果蝇组织中的肌动球蛋白分布的已知模式。我们在数值模拟中表明，只有当胚胎的几何形状呈现出一些精确的特征时，才能获得正确的运动。这意味着负责这些特征的先前形态发生运动需要成功才能进行下一轮形态发生。这突出了机械反馈对形态发生程序的贡献，以及机械作用如何在整个胚胎的规模上整合。
Downstream of gene expression, effectors such as the actomyosin contractile machinery drive embryo morphogenesis. During Drosophila embryonic axis extension, actomyosin has a specific planar-polarised organisation, which is responsible for oriented cell intercalation. In addition to these cell rearrangements, cell shape changes also contribute to tissue deformation. While cell-autonomous dynamics are well described, understanding the tissue-scale behaviour challenges us to solve the corresponding mechanical problem at the scale of the whole embryo, since mechanical resistance of all neighbouring epithelia will feedback on individual cells. Here we propose a novel numerical approach to compute the whole-embryo dynamics of the actomyosin-rich apical epithelial surface. We input in the model specific patterns of actomyosin contractility, such as the planar-polarisation of actomyosin in defined ventro-lateral regions of the embryo. Tissue strain rates and displacements are then predicted over the whole embryo surface according to the global balance of stresses and the material behaviour of the epithelium. Epithelia are modelled using a rheological law that relates the rate of deformation to the local stresses and actomyosin anisotropic contractility. Predicted flow patterns are consistent with the cell flows observed when imaging Drosophila axis extension in toto, using light sheet microscopy. The agreement between model and experimental data indicates that the anisotropic contractility of planar-polarised actomyosin in the ventro-lateral germband tissue can directly cause the tissue-scale deformations of the whole embryo. The three-dimensional mechanical balance is dependent on the geometry of the embryo, whose curved surface is taken into account in the simulations. Importantly, we find that to reproduce experimental flows, the model requires the presence of the cephalic furrow, a fold located anteriorly of the extending tissues. The presence of this geometric feature, through the global mechanical balance, guides the flow and orients extension towards the posterior end. The morphogenesis of living organisms is a facinating process during which a genetic programme controls a sequence of molecular changes which will cause the original embryo to acquire a new shape. While we have a growing knowledge of the timing and spatial distribution of key molecules downstream of genetic programmes, there remain gaps of understanding on how these patterns can generate the appropriate mechanical force, so as to deform the tissues in the correct manner. In this paper, we show how a model of tissue mechanics can link the known pattern of actomyosin distribution in Drosophila tissues to the process of axis extension, which is a ubiquitous morphogenetic movement of developing animal embryos. We show in numerical simulations that the correct movement is obtained only if the geometry of the embryo presents some precise features. This means that prior morphogenetic movements responsible for these features need to have succeeded in order to carry on the next round of morphogenesis. This highlights the contribution of mechanical feedback on the morphogenetic programme and also how mechanical action integrates at the scale of the whole embryo.