DROSOPHILA GUIDANCE · Imaging of border cell migration and receptor tyrosine kinase signalling in live Drosophila ovaries
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-08-01 → 2007-07-31
- EU contribution
- €148,588
- Participants
- 1
- Scheme
- EIF
Lines connect the coordinator with its partners.
Results in brief
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.
Data: CORDIS, © European Union
Project objective
The mechanism by which cells migrate is well understood in vitro but far less is known about how invasive migration occurs within a three dimensional tissue. Migration of border cells in the Drosophila ovary provides excellent model system for this. Border cells delaminate from an epithelium surrounding the germ line tissue and migrate, as an 8-cell cluster, directionally towards the oocyte. To migrate, border cells must actively invade the germ line tissue. Studying their migration may therefore provide better understanding of how cancer cells metastasise.Genetic studies have defined signalling molecules involved in guiding the migration: Two Receptor Tyrosine Kinases, PVR (PDGF/VEGF Receptor) and EGFR, act as guidance receptors. A small GTPase, Rac, and sp ecific Rac exchange factors, act downstream of the receptors. Studies of fixed tissues have also given some insight into the mechanism of migration: One border cell within the cluster initiates migration by extending a very long cellular extension (LCE) in the direction of migration. LCEs may provide the mechanical force for migration, pulling the border cell cluster towards the oocyte. What is missing for understanding the mechanism of spatially controlled guidance signalling and mechanism of movement i s to visualize these events dynamically.I propose to develop a method of culturing and imaging Drosophila ovaries in order to observe border cell migration in real time. I will observe the behaviour of border cells and their LCEs in live ovaries to determine how the cell cluster translocates. I will also construct Fluorescence Resonance Energy Transfer (FRET) constructs to monitor the activities of the PVR and EGFR receptors, as well as Rac activity. This will allow me to study the spatial activation of RTK signalling and Rac activity in real time. Finally, I intend to apply the tools I generate to other models of motility, such as migration of hemocytes in the Drosophila embryo.
Original text from CORDIS.
Participants
- EUROPEAN MOLECULAR BIOLOGY LABORATORY · HEIDELBERGCoordinatorGermany
Links
Data: CORDIS, © European Union