Final Activity Report Summary - DROSOPHILA GUIDANCE (Imaging of border cell migration and receptor tyrosine kinase signalling in live Drosophila ovaries) Cell migration is required for many processes in life. While the embryo grows, cells often need to change places or move to different locations. In adults, cells of the immune system must migrate to the site of infection and skin cells must migrate to heal wounds. The process of migration must, however, be tightly regulated. Inappropriate migration leads to cancer metastasis, allowing cancer cells to spread throughout the body, with fatal consequences. Cells can migrate either alone or as groups, both normally and in cancer. It is this group migration that we were interested in studying. To understand the positive and negative aspects of cell migration we used the fruit fly, drosophila melanogaster, as a model system. We followed a small group of cells, border cells, which performed a highly predictable, guided migration in the fly ovary. These cells moved as a group, invading neighbouring tissue to end up next to the oocyte, the cell which would go on to form an egg. This invasive migration was reminiscent of cancer metastasis, as cells had to break away from their neighbours and then push their way through other cells, which were tightly stuck together, to reach their destination. We developed an imaging method, which enabled us to watch this migration process live. This allowed us, in combination with the numerous genetic tools, to study how this group of cells moved as a unit. We found, surprisingly, that these cells moved by two different methods of locomotion. Firstly, the group was led by one cell, which effectively pulled the rest of the cluster along. Later in migration, the cells took a more 'democratic' approach, with many cells taking part in the migration and all of them apparently playing a role in deciding in which direction to move. By the project completion we were testing whether this novel paradigm was also applicable to other migrating systems.