Robustness and plasticity of epithelial architectures

"Animal cells display characteristic, cell-type specific shapes that are precisely adapted to cell function. Cell shape alterations are a hallmark of pathology, commonly used in diagnostics. Yet, cells can also rapidly change shape in response to molecular or mechanical signals. How the balance between cell shape stability and plasticity is achieved is not understood. Tight coupling between shape robustness and function is particularly important in epithelial cells, which adhere to each other to form protective sheets between the organism and the external world. Epithelia can form simple squamous, cuboidal or columnar sheets or become multilayered, depending on their function. Despite the importance of epithelial organisation, the mechanisms controlling epithelial cell shapes and architectures remain elusive.This proposal will investigate the regulation, robustness and function of epithelial cell shapes and architectures. Our central hypothesis is that epithelial cells occupy a ""morphogenetic landscape"" with stable shapes that are at the same time poised to rapidly change in response to stimuli. We will establish a cross-disciplinary research programme, combining molecular cell biology, quantitative biophysics, advanced imaging, modelling and epithelial mechanobiology to address this hypothesis. Using in vitro models as well as Drosophila and mouse in vivo epithelia, we will uncover the molecular and mechanical mechanisms of shape specification and plasticity, and the biomechanical basis of morphological transitions in epithelia. We will then explore how these morphological transitions are adapted to drive emergence of multilayered epithelia, required for barrier function in vertebrates. Finally, we will interrogate feedbacks between morphogenesis and fate specification in epithelial cells. Our synergistic collaboration will reveal how epithelial architectures emerge and evolve, and unveil fundamental principles of the cross-talk between cell shape and fate."