Coordination of morphogenetic actions across the entire organism

在多细胞生物的发育过程中，上皮细胞的折叠是形成器官原基或部分器官的一种广泛应用的机制。在果蝇胚胎的原肠胚形成过程中，中胚层的内陷是上皮折叠的一个很好的研究例子。过去的研究主要集中在理解上皮折叠的遗传控制和识别控制负责细胞形状变化的亚细胞事件的分子，而现在对信号级联、连接的作用和参与该过程的细胞骨架网络有了更多的了解。然而，在上皮环境下，这些收缩细胞构成了更高层次的细胞组合的一部分，它们的行为必须与它们直接附着的细胞以及更远的邻居协调。该项目的目的是研究收缩细胞彼此之间以及与周围细胞相互作用的方式，确定细胞的哪些特性允许细胞的组装行为，从而使收缩引起的扭曲以一种生产方式影响胚胎的其余部分，最后确定它们彼此机械连接的方式如何影响它们的行为。我们已经建立了一种在高时间和空间分辨率下成像整个发育中的胚胎细胞形状的方法。这使我们能够精确地将不同细胞群的行为联系起来，并得出因果关系的结论。然后，这些可以通过基因和物理操作进行测试。例如，我们能够将细胞固定在给定的位置，或者可以用激光切断连接。细胞的整体行为可以通过遗传手段加以改变。

The folding of epithelial sheets is a widely used mechanism to create organ primordia or parts of organs during the development of multicellular organisms. The invagination of the mesoderm during gastrulation in the Drosophila embryo is a well-studied example of an epithelial folding. Studies in the past have focused on understanding the genetic control of epithelial folding and identifying the molecules that control the subcellular events responsible for the cell shape changes, and much is now known about the signalling cascades, the role of junctions and the cytoskeletal networks involved in the process. However, these constricting cells form part of a higher order assembly of cells in an epithelial context, and their actions must be coordinated with those cells to which they are directly attached, and their more distant neighbours. The aim of this project is to investigate the way in which the constricting cells interact with each other and with their surrounding cells, to determine what the properties of the cells are that allow the assembly of cells to behave such that the distortion caused by constriction affects the rest of the embryo in a productive manner, and finally, to determine how the way in which they are mechanically linked to each other influences their behaviours. We have established a way of imaging cell shapes throughout the developing embryo at high temporal and spatial resolution. This enables us to correlate precisely the behaviours of different cell population and draw conclusions about causalities. These can then be tested by genetic and physical manipulations. For example, we are able to fix cells in a given position, or connections can be severed by laser. Overall cell behaviour can be modified by genetic means.