Epithelial Sheet Dynamics during Primitive Streak Formation as Active Matter

作为活性物质的原条形成过程中的上皮片动力学

• 批准号: BB/N009789/1
• 负责人: Kees Weijer
• 金额: $ 54.45万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN009789%2F1
• 关键词: Epithelial; Sheet; Dynamics; during; Primitive

An important goal of the study of development of higher animals including humans is understanding gastrulation. Gastrulation is a critical stage in early embryonic development where the main body plan of the embryo is laid down and the main body axes emerge. It involves large-scale, long-range cell movements during which cells of the three tissue layers, the ectoderm, the mesoderm and endoderm take up their correct positions in the embryo. The endoderm is located innermost in the embryo and adult, lining the digestive tract and associated glands. It is surrounded by the mesoderm that will give rise to the muscles and the skeleton, which is in turn covered by the outmost layer, the ectoderm, which will form the epidermis and the nervous system. Defects in cell movements during gastrulation result in severe cases in death and in less severe cases form the basis of many birth defects.The cellular processes and chemical signalling underlying gastrulation in higher vertebrates (such as humans) are experimentally studied in so-called model systems, especially chick and mouse embryos. The chick embryo has the advantage that development takes place outside the mother and is therefore easily experimentally accessible. It is also flat and translucent which helps observation of cell movement during gastrulation. Gastrulation in chick embryos greatly resembles gastrulation in humans, which means that findings can be extrapolated to human development. During very early stages development the chick embryo consists of two concentric disks of tissue sitting on top of the yolk; the inner, one cell layer thick, ring will form the embryo proper. Cells in a sickle shaped domain on one side of this epiblast disc will differentiate into the mesoderm and endoderm. During gastrulation this sickle shaped domain of mesendoderm cells deforms into a stripe of tissue extending from one edge of the embryo through the central midline; the structure is known as the primitive streak. The central cells of the primitive streak then move inwards and away from this site of ingression to form the inner mesodermal and endodermal layers of the embryo.In this project we will study gastrulation in the chick embryo using two complementary approaches. First, we use experiments to follow the mechanical and chemical cell-to-cell signalling in the developing embryo at a cell-level detail. In order to do so we have developed and built a novel type of microscope, a light-sheet fluorescence microscope, that allows us to see almost all the cells in the embryo (50,000-200,000) in a special chick strain in which the cell membranes of all cells are marked with a green fluorescent protein. We study how different cell behaviours such as division, shape changes and motion are coordinated to generate these tissues and which chemical and mechanical cell-cell signalling mechanisms control them. Second, we build a computational model based on active, interacting cells using concepts from the physics of collective motion and use it to understand cell flow both at the local and the full embryo scale. Our study of the interplay between cell-cell signalling, cell differentiation, proliferation and migration is not only important to the community of researchers whose interest is focused on embryogenesis but will also be of great importance to scientists whose research is centred on processes such as wound healing, tissue repair and regeneration. Furthermore, in order to progress with the proposed research we will develop several new mathematical and computational techniques which are expected to be of great value for further mathematical investigation of other biological and biomedical/engineering problems.

研究包括人类在内的高等动物发育的一个重要目标是了解原肠胚形成。原肠胚形成是早期胚胎发育的关键阶段，胚胎的主体平面被奠定并出现主体轴。它涉及大规模、长距离的细胞运动，在此期间，三个组织层的细胞，即外胚层、中胚层和内胚层，在胚胎中占据它们的正确位置。内胚层位于胚胎和成体的最里面，衬在消化道和相关的腺体上。它被中胚层包围，中胚层将产生肌肉和骨骼，而骨骼又被最外层外胚层覆盖，外胚层将形成表皮和神经系统。原肠胚形成过程中细胞运动的缺陷导致严重的死亡病例，在不太严重的情况下形成许多出生缺陷的基础。高等脊椎动物（如人类）原肠胚形成的细胞过程和化学信号在所谓的模型系统中进行了实验研究，特别是鸡和小鼠胚胎。鸡胚的优点是发育发生在母体之外，因此很容易通过实验获得。它也是平的和半透明的，这有助于观察原肠胚形成期间的细胞运动。鸡胚的原肠胚形成与人类的原肠胚形成非常相似，这意味着这些发现可以外推到人类发育中。在非常早期的发育阶段，鸡胚由位于蛋黄顶部的两个同心圆的组织盘组成;内环，一层细胞厚，将形成胚胎。在该上胚层盘的一侧上的镰刀形区域中的细胞将分化成中胚层和内胚层。在原肠胚形成期间，中内胚层细胞的这种镰刀形区域变形为从胚胎的一个边缘延伸通过中央中线的组织条纹;该结构被称为原始条纹。原始条纹的中央细胞然后向内移动，远离这个侵入的位置，形成胚胎的内中胚层和内胚层层。在这个项目中，我们将使用两种互补的方法研究鸡胚的原肠胚形成。首先，我们使用实验来跟踪细胞水平细节的发育胚胎中的机械和化学细胞间信号传导。为了做到这一点，我们开发并制造了一种新型的显微镜，一种光片荧光显微镜，它使我们能够在一种特殊的鸡种中看到胚胎（50，000 - 200，000）中的几乎所有细胞，其中所有细胞的细胞膜都用绿色荧光蛋白标记。我们研究不同的细胞行为，如分裂，形状变化和运动是如何协调产生这些组织，以及化学和机械细胞信号机制控制它们。其次，我们使用集体运动物理学的概念，建立了一个基于活跃的相互作用的细胞的计算模型，并使用它来理解局部和全胚胎规模的细胞流动。我们对细胞间信号传导、细胞分化、增殖和迁移之间相互作用的研究不仅对关注胚胎发生的研究人员很重要，而且对研究集中在伤口愈合、组织修复和再生等过程的科学家也很重要。此外，为了与拟议的研究进展，我们将开发几个新的数学和计算技术，预计将是其他生物和生物医学/工程问题的进一步数学研究的巨大价值。

项目成果

Generating active T1 transitions through mechanochemical feedback

通过机械化学反馈产生活跃的 T1 转变

• DOI: 10.48550/arxiv.2106.12394
• 发表时间: 2021
• 期刊: arXiv e-prints
• 作者: Sknepnek Rastko

Dynamical patterns in active nematics on a sphere

球体上活性向列的动态模式

• DOI: 10.48550/arxiv.1705.05166
• 发表时间: 2017
• 作者: Henkes S

Coordinated tractions increase the size of a collectively moving pack in a cell monolayer

协调的牵引力增加了单层细胞中集体移动包的尺寸

• DOI: 10.1016/j.eml.2021.101438
• 发表时间: 2021
• 期刊: Extreme Mechanics Letters
• 影响因子: 4.7
• 作者: Saraswathibhatla, Aashrith;Henkes, Silke;Galles, Emmett E.;Sknepnek, Rastko;Notbohm, Jacob
• 通讯作者: Notbohm, Jacob

The evolution of gastrulation morphologies.

胃形态的演变。

• DOI: 10.1242/dev.200885
• 发表时间: 2023-04-01
• 期刊: Development (Cambridge, England)

Estimating stresses driving tissue flows using a stokes inverse problem

使用斯托克斯逆问题估计驱动组织流动的应力

• DOI: 10.1080/00207160.2022.2152281
• 发表时间: 2022
• 期刊: International Journal of Computer Mathematics
• 影响因子: 1.8
• 作者: Gao Y