Prostaglandins regulate invasive, collective border cell migration

Abstract

AbstractWhile prostaglandins (PGs), short-range lipid signals, regulate cell migration, their mechanisms of action are poorly understood in collective migration. To address this, we useDrosophilaborder cell migration during Stage 9 of oogenesis. The border cells delaminate from the epithelium, and migrate collectively and invasively between the nurse cells. Pxt is theDrosophilacyclooxygenase-like enzyme responsible for all PG synthesis. Loss of Pxt results in both a significant delay in border cell migration during Stage 9 and an increase in cluster length compared to wild-type controls. Contributing to these phenotypes is altered integrin localization. Integrins are enriched on the border cell membranes, and this enrichment is lost inpxtmutants. Active integrins require interaction with the actin cytoskeleton. As we previously found PGs regulate the actin bundler Fascin and Fascin is required for border cell migration, we hypothesized PGs regulate Fascin to control integrins. Supporting this, loss of Fascin results in apxt-like integrin localization, and dominant genetic interaction studies reveal that co-reduction of Pxt and Fascin results in delayed and elongated border cell clusters. Together these data lead to the model that PG signaling controls Fascin, and thereby integrins, to mediate on-time border cell migration and maintain cluster cohesion.