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，这些细胞通过侧向粘附接触相互粘附，形成称为上皮的薄片。在这些表中，单元格都指向同一个方向。因此，上皮呈现两个不同的表面-顶表面和底表面。这种上下方向是重要的，因为它支持上皮细胞控制营养物（肠）、氧气（肺）的吸收或盐和毒素（肾或肝）的过滤的能力。除了这种上下方向，上皮细胞也采用特定的形状。当一个上皮层自我闭合时，它就形成了一个管或腔。食管、肠、肺、肾和胃都是管状上皮结构。通过这项新的研究计划，我们将研究细胞如何协调其形状的变化，以产生这些对器官功能至关重要的结构。通常，上皮细胞是通过内力产生机制和外部约束（包括机械约束）的组合来成形的，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已经确定了一种新的收缩机制，它可以驱动上皮细胞底面的减少，使整个组织形成圆顶。在这里，我们将介绍器官形成中的这种新的收缩机制。此外，为了了解是什么引起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以协调它们的收缩。我们最近的研究表明，细胞之间的钙流促进了这种协调。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底收缩。总之，我们希望我们的工作建立新的途径，上皮组织形状控制，广泛相关的上皮组织发育，支持器官功能至关重要的我们的理解。

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.