Supracellular coordination in tissue morphogenesis

How organ shape is genetically encoded remains a major unresolved question in biology. All tissues arise from simple primordia that become patterned through transcriptional changes within individual cells. Since organ form drives tissue function, revealing how cell-specific transcriptional changes trigger biochemical events at the nanometre-scale within individual cells that in turn result in highly coordinated changes of many cells at the tissue or micro-to-millimetre-scale is essential to understanding organ physiology. We leverage two complementary models of tube morphogenesis to understand supracellular coordination in morphogenesis. Most internal organs are epithelial and tubular, and failure in tube formation or homeostasis can lead to severe malformations and is the cause of most cancers. We combine as models the simple but highly tractable budding-morphogenesis of the salivary glands in the Drosophila embryo with the formation of a human tubular organ with great clinical importance, nephron morphogenesis in human renal organoids. Using a combination of quantitative imaging, physical interference, advanced genetic tools and sequencing approaches that we have established in both models, we will assess how coordination is implemented through supracellular cytoskeletal assemblies (RQ1), how cytoskeletal crosstalk mediates tissue-wide coordination (RQ2) and how the transcriptional blueprint establishes non-transcriptional coordination and feed-back through tissue mechanics (RQ3).