Final Report Summary - JTOMO (Study of the molecular organization of cell junctions by cryo-electron tomography)
Cell-cell junctions are involved in developmental events, cell migration and cell proliferation. In this project we analysed the structure and interplay of the cell-cell junction on the example of the epidermal closure in Drosophila melanogaster. For this we reconstructed a model closure event, the dorsal closure in fly embryos, by large-volume correlative electron tomography. The comprehensive and quantitative analysis of the interplay of the adherens junctions with the cytoskeletal components shows the basis enabling initially separated epidermal cells to seal the epithelium. The mechanism for this involves the initial adherens junction formation between opposite cells, and then a cortical accumulation of shrinking microtubules that pull on those in order to seal the epidermis. It turned out that we have rediscovered a force generation mechanism already been known to happen during mitotic spindle positioning, but as a completely new concept for tissue sealing and wound healing. Our algorithmic developments were fuelling the biological findings, which would not have been possible without improved reconstruction and newly introduced validation methods, which we pioneered over the previous years during our ERC funding.