Mechanisms of cell coordination in epithelial morphogenesis analyzed by quantitative 3D imaging

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During embryonic development and tissue repair, cells move over long distances and undergo dramatic changes in shape, and in so doing, they push, pull and deform their neighbors. Therefore, an exquisite degree of coordination is necessary to preserve the integrity of tissues when cells move or generate physical forces. Although the main molecular players involved in force generation are known, the mechanisms by which cells coordinate their behaviors remain a mystery, mainly because it is difficult to establish the initial events that trigger cells to act together. Notably, wound healing in embryos of many different species is driven by the coordinated generation of force by the cells adjacent to the wound. In wound healing one can clearly establish and deliver at will the signal that induces cell coordination (the wound), making it an ideal system to investigate the mechanisms of coordinated force generation. We propose to investigate the physical and molecular mechanisms of cell coordination using wound repair in Drosophila embryos as a model system. We will do these through 3 projects in which we will take advantage of the powerful live imaging and genetic tools available in Drosophila, and of our previous experience developing quantitative image analysis tools and biophysical methods to locally manipulate forces in embryos. This research program will be pioneer in Canada in the establishment and application of biophysical methods, including magnetic tweezers or laser ablation, for their use in living organisms, as well as in the creation of new of tools for high-throughput, microscopy-based screening that will be of use to other researchers. Completing these aims will also serve the purpose of providing 3 Ph.D. students and several summer students with training in the areas of image analysis, biophysics, and cell and developmental biology. Trainees with this multidisciplinary background are currently in high demand in Canada, both in academia and in industry (biotech, pharmaceutical, software engineering).