Cell fate to mechanical cellular properties: coordinated cell behaviours during Drosophila gastrulation

细胞命运与细胞机械特性：果蝇原肠胚形成过程中协调的细胞行为

• 批准号: 452556219
• 负责人: Professorin Dr. Maria Leptin, Ph.D.
• 金额: --
• 依托单位: Institut für Genetik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/452556219?language=en
• 关键词: Cell; fate; mechanical; cellular; properties

During the development of an organism, cells change their shapes in many ways to contribute to the creation of tissues and organs. A common way of creating complex shapes in animals is the folding of two-dimensional, flat epithelia into three-dimensional higher order structures. A particularly well studied example for this is the formation of the ‘ventral furrow’, the first morphogenetic event during the early development of the Drosophila embryo. We know the genes and the mechanisms that trigger a contraction of the cells that form the furrow, which results to an indentation in the epithelium. Much less is known about how cells outside the furrow participate in the process, and thereby enable it. We have discovered differences in the mechanical properties of different cell populations in the embryo, and found that these differences matter for the proper formation of the furrow. But we do not understand the molecular or biochemical basis. The aim of this project is to discover it.The mechanical properties of the cells in the embryo are determined by the proteins in each cell. For many proteins it is not only the presence or absence (or precise level) that may matter, but also their state of activity, which is in turn controlled by other proteins. If two hypothetical cells that are identical in all respects apart from their mechanical properties, they should differ only, or at least mainly, in those protein activities that govern mechanical properties. This is the assumption on which our proposal is based, and it is these proteins that we aim to identify. The early Drosophila embryo is an ideal system for this because up to the period of gastrulation, the 6000 cells of the embryo contain more or less identical sets of proteins. We will find the proteins that are of interest to us by determining the entire set of proteins in each of three cell populations along the dorso-ventral axis that represent the populations participating in furrow formation. We will then compare these sets, as well as markers for the state of activity of the proteins in each set. Not all of the proteins we may find that differ between the populations will necessarily be directly involved in cell mechanics. We will select proteins for detailed study based on further assumptions, for example that components of the cytoskeleton and cell adhesion complexes play the most important roles in determining mechanical cell properties. Classic and novel genetic methods will then be used to manipulate these proteins in the embryo, and assess they outcomes of these manipulations, as a means of testing our hypotheses.

在生物体的发育过程中，细胞以多种方式改变其形状，以促进组织和器官的形成。在动物中产生复杂形状的常见方式是将二维扁平上皮折叠成三维高阶结构。一个特别好的研究例子是“腹沟”的形成，这是果蝇胚胎早期发育过程中的第一个形态发生事件。我们知道触发形成沟槽的细胞收缩的基因和机制，这导致上皮中的凹陷。对于沟外的细胞如何参与这一过程，从而使其得以实现，我们所知甚少。我们发现胚胎中不同细胞群的机械特性存在差异，并发现这些差异对沟的正确形成至关重要。 但我们不了解分子或生物化学基础。这个项目的目的就是发现它。胚胎中细胞的机械特性是由每个细胞中的蛋白质决定的。对于许多蛋白质来说，不仅存在或不存在（或精确水平）可能很重要，而且它们的活性状态也很重要，而活性状态又由其他蛋白质控制。如果两个假设的细胞除了它们的机械性质外在所有方面都是相同的，那么它们应该只在或至少主要在那些控制机械性质的蛋白质活性上不同。这是我们的建议所基于的假设，我们的目标是识别这些蛋白质。早期的果蝇胚胎是一个理想的系统，因为直到原肠胚形成时期，胚胎的6000个细胞含有或多或少相同的蛋白质组。我们将通过确定沿沿着轴的三个细胞群体中的每一个中的整套蛋白质来找到我们感兴趣的蛋白质，所述细胞群体代表参与沟形成的群体。然后，我们将比较这些集合，以及每个集合中蛋白质活性状态的标记。并不是所有的蛋白质，我们可能会发现，不同的人口将必然直接参与细胞力学。我们将根据进一步的假设选择蛋白质进行详细的研究，例如，细胞骨架和细胞粘附复合物的组分在确定细胞机械特性中起着最重要的作用。然后将使用经典和新颖的遗传方法来操纵胚胎中的这些蛋白质，并评估这些操纵的结果，作为测试我们假设的一种手段。