Pulled in the Wrong Direction

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Developing Drosophila egg chambers consist of germline cells (the oocyte and nurse cells) surrounded by somatic epithelial follicle cells. During development, a group of epithelial cells, the border cells, detach from the epithelium and, guided by secreted growth factors, migrate as a cluster toward the oocyte. Prasad and Montell performed time-lapse video imaging of migrating border cells in organ culture to investigate the dynamics of border cell migration in response to guidance factors. They confirmed previous research from fixed tissue indicating that border cell migration was inhibited in egg chambers coexpressing dominant-negative forms of the PVR (platelet-derived growth factor/vascular endothelial growth factor receptor) and EGFR (epidermal growth factor receptor) receptor tyrosine kinases. Further, they discovered that, rather than inhibiting the extension of actin-rich protrusions in the direction of migration (as seen in wild-type cells), these mutant receptors elicited substantial numbers of protrusions pointing away from the direction of migration. Cells expressing constitutively active EGFR failed to extend protrusions or detach from the epithelium; cells expressing constitutively active PVR did extend protrusions but also failed to detach. A dominant-negative form of Kuzabian, a metalloproteinase involved in Notch activation (which is necessary for normal border cell migration), elicited a decrease in the frequency of protrusions and an increase in their lifetime and also inhibited detachment from the epithelium. The authors conclude that, rather than stimulating actin polymerization and the formation of protrusions at the leading edge of migrating border cells, guidance receptor signaling provides directionality by inhibiting the extension of protrusions in the wrong direction. M. Prasad, D. J. Montell, Cellular and molecular mechanisms of border cell migration analyzed using time-lapse live-cell imaging. Dev. Cell 12 , 997-1005 (2007). [PubMed]