Fluorescence microscopy image showing a cluster of border cells (blue nuclei, one cell labeled green) inside the ovary of the fruit fly Drosophila melanogaster
Cell migration—the orchestrated movement of cells from one location to another—is a key process in animal development. It plays important roles in tissue formation and immune response, as well as cancer metastasis. However, although scientists have performed extensive studies on the migration of individual cells, they still lack a detailed understanding of collective cell migration.
The fruit fly Drosophila melanogaster is one of several model organisms scientists use for studying cell migration. In the ovary of this fruit fly, a cluster of specialized border cells (pictured) detach from the epithelium and migrate to the oocyte. To reach their destination, border cells undergo collective migration in a way that allows them to squeeze between the giant nurse cells in the space between the epithelium and oocyte.
Previous studies have identified two cell-surface receptors, namely platelet-derived growth factor/vascular endothelial growth factor–related receptor (PVR) and epidermal growth factor receptor (EGFR), to be important for border cells. These receptors read guidance cues from their environment in order to direct border cells to the oocyte. Pernille Rørth and co-workers at the A*STAR Institute of Molecular and Cell Biology and the National University of Singapore have now found that the two receptors change the behavior of border cells in different ways in order to steer the collective migration in the right direction.
The researchers studied the effects of PVR and EGFR on border cells using a combination of live imaging and RNA interference techniques, which reduce the expression of either PVR or EGFR in border cells. This approach allowed them to obtain quantitative information about the behavior of border cells. They found that PVR and EGFR both promote the maintenance and growth of front extensions, which in turn leads to more forward movement of the cell cluster. PVR and EGFR signaling also ensure that the extensions of cells at the front are productive and ‘sticky’, whereas extensions of cells at the back are not.
The researchers also noted functional differences between PVR and EGFR. They found that PVR induces a sliding behavior, whereas EGFR induces a tumbling behavior. In essence, PVR appears to be a better guidance receptor than EGFR.
“We have previously identified the cues and receptors that are responsible for directional movement,” says Rørth. “Now we have shown how they do the job—how the guidance signals change cell behavior such that cells move in the right direction.” The researchers suggest that EGFR may be optimized for cell-wide or nuclear responses, whereas PVR may be optimized for more local or polarized responses.
The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology.
