Dr Tim Fessenden

Developing tissues change shape and tumors initiate spreading through collective cell motility. Despite a wealth of knowledge on individual cell migration in 3D matrices, conserved mechanisms by which tissues initiate motility into their surroundings are not known. We investigated cytoskeletal regulators during collective invasion by tumor organoids and epithelial Madin–Darby canine kidney (MDCK) spheroids undergoing branching morphogenesis in collagen. Inhibiting formins, but not the Arp2/3 complex, prevented the formation of migrating cell fronts in both cell types. Depleting the formin Dia1 in MDCK cells did not alter planar cell motility either within spheroids or in 2D scattering assays. However, Dia1 was required to stabilize protrusions extending into the collagen matrix. Live imaging of actin, myosin, and collagen in wild type spheroids revealed myosin-rich adhesions that deformed individual collagen fibrils and generated large traction forces, whereas Dia1-depleted spheroids exhibited unstable adhesions and lower force generation. This work delineates focal adhesions that drive planar cell motility from those required for tissue shape changes, and describes the cytoskeletal architecture on which these adhesions rely. Ongoing work considers how dendritic cells, sentinel cells of the immune system, migrate through confluent tissues such as tumors to survey for damage. At short timescales, dendritic cells must translocate through tissues, while at timescales of days, they must redistribute from sites of tissue damage to draining lymph nodes. Intravital imaging of dendritic cells inside tumors shows profound changes in dendritic cell migration over the course of tumor progression, which may restrain anti-tumor immunity