Border cells in the Drosophila ovary originate within an epithelium, detach from it, invade neighboring nurse cells, and migrate as a coherent cluster. This migration has served as a useful genetic model for understanding epithelial cell motility. The prevailing model of growth factor-mediated chemotaxis in general, and of border cells in particular, posits that receptor activation promotes cellular protrusion at the leading edge. Here we report the time-lapse video imaging of border cell migration, allowing us to test this model. Reducing the activities of the guidance receptors EGFR and PVR did not result in the expected inhibition of protrusion, but instead resulted in protrusion in all directions. In contrast, reduction in Notch activity resulted in failure of the cells to detach from the epithelium without affecting direction sensing. These observations provide new insight into the cellular dynamics and molecular mechanisms of cell migration in vivo.