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

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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.