NANOMORPH: In vivo investigation of the mechanistic roles of epithelial cell vertices in morphogenesis at the nanometre scale

Epithelial sheets are remarkably dynamic: during embryonic development, cells change position as cell sheets grow and change shape. Cell rearrangements are a challenge for epithelia, as cell-cell junctions need to remodel, while at the same time preserving mechanical strength to maintain the integrity of the cell sheet. Recently, tricellular junctions, where three cells meet, are emerging as potential organisers of cell-cell junction remodelling during morphogenesis. Specialised components at tricellular junctions have been identified but their functions in morphogenesis are unclear. We have discovered a new component of tricellular junctions, the transmembrane adhesion molecule Sidekick. Sidekick concentrates at tricellular adherens junctions and at the centre of epithelial rosettes in fly epithelia, sites we call here "epithelial cell vertices". We propose to use Drosophila as a model and Sidekick as a molecular entry point to i) elucidate the organisation of epithelial cell vertices at the nanometre scale, using super-resolution microscopy (PAINT) in the intact embryo and ii) solve the mechanisms by which epithelial cell vertices control junctional dynamics during cell rearrangements and other morphogenetic cell behaviours. To leverage new knowledge from Drosophila about epithelial cell vertices, we will investigate the function of Sidekick molecules in vertebrate morphogenesis, using the zebrafish model.