Coordinating tissue surface contraction and basement membrane reorganisation to shape an organ in three-dimensions

我们的大多数器官都含有细胞，它们通过侧向粘连接触相互粘连，形成被称为上皮的片状细胞。在这些工作表中，所有单元格都指向同一方向。因此，上皮有两个截然不同的表面--顶面和底面。这种自上而下的取向很重要，因为它支持上皮细胞控制营养物质(肠道)、氧气(肺)的吸收或盐和毒素(肾脏或肝脏)的过滤。除了这种自上而下的取向外，上皮还具有特殊的形状。当上皮片自身闭合时，就会形成管状或空洞。食道、肠、肺、肾、胃均为管状上皮结构。有了这个新的研究方案，我们将研究细胞如何协调它们形状的变化来产生这些对器官功能至关重要的结构。通常情况下，上皮是通过内力产生机制和外部约束(包括机械约束)组合形成的，内力产生机制为细胞变形提供动力。我们实验室最近的工作发现了一种新的收缩机制，它可以推动上皮细胞底部表面的缩小，将整个组织塑造成穹顶。在这里，我们将描述器官形成中这种新的收缩机制的特征。此外，为了了解是什么导致了整个基底组织表面的收缩，我们还需要确定细胞如何相互作用来协调它们的收缩。我们最近的工作表明，细胞间的钙离子流动促进了这种协调。我们将确定这些钙流是如何产生的，以及它们如何调节细胞的基础收缩。总之，我们希望我们的工作在上皮组织形状控制中建立新的途径，这将与我们对上皮组织发育的理解广泛相关，对支持器官功能至关重要。

Most of our organs contain cells that adhere to one another through lateral adhesion contacts to form sheets, called epithelia. In these sheets, cells all point in the same direction. Therefore, an epithelium presents two distinct surfaces - a top and a bottom surface. This top-bottom orientation is im-portant because it underpins the ability of epithelia to control the absorption of nutrients (intestine), oxygen (lung) or the filtration of salts and toxins (kid-ney or liver). In addition to this top-bottom orientation, epithelia also adopt specific shapes. When an epithelial sheet closes onto itself, it forms a tube or cavity. The oesophagus, intestine, lung, kidney and stomach are all tubu-lar epithelial structures. With this new research proposal, we will investigate how cells coordinate changes in their shape to generate these structures, vital for organ function. Typically, epithelia are shaped through a combination of internal force-generating machineries, which power cell deformation, and external constraints, including mechanical. Recent work in our laboratory has identified a novel contractile machinery that can power the reduction of the bottom surface of an epithelium, to shape the whole tissue as a dome. Here, we will characterise this new contractile machinery in organ formation. Moreover, to understand what induces contraction of the basal tissue surface as a whole, we will also need to determine how cells interact to coordinate their contraction. Our recent work indicates that calcium fluxes between cells promote this coordination. We will determine how these calcium fluxes are generated and how they regulate cell basal contraction. Altogether, we expect our work establishing new pathways in epithelial tissue shape control, to be broadly relevant to our understanding of epithelial tissue development, vital to supporting organ function.