78 Oral - Cell Biology II
Friday April 08, 12:00 PM - 12:15 PM

Authors:
Samuel Mellentine; Anna Ramsey; Omar Rabab'h; Tina Tootle

Affiliation: University of Iowa Carver College of Medicine

Keywords:
r. cell migration; l. lipids in signaling

Collective cell migration – the coordinated movement of associated cells – is important for both normal development and tumor invasion. Prostaglandins (PGs) are short-range lipid signals that regulate cell migration and are up regulated in many cancers. However, their mechanisms of action during collective migration are poorly understood. Here we use the native, collective migration of the Drosophila border cells to uncover the roles of PGs. During Stage 9 of oogenesis a cluster of epithelial cells becomes specified as border cells, delaminates from the epithelium, and migrates collectively and invasively between the nurse cells. Prior work found that loss of Pxt, the Drosophila cyclooxygenase-like enzyme responsible for all PG synthesis, results in delayed migration and decreased cluster cohesion. However, the particular PG or PGs controlling border cell migration remain unknown. To begin to address this, we assessed the roles of three PGE₂ synthases, (mPGES-1, mPGES-2, and cPGES) and the sole PGF_2α synthase (PGFS) in border cell migration. Our data support the model that cPGES and PGFS are required for on-time border cell migration. Specifically, loss of cPGES or PGFS delays border cell migration, but has no effect on cluster cohesion. We are currently using cell-specific RNAi knockdown to determine which cells produce PGE₂ and PGF_2α. Initial studies suggest that, cPGES acts in the nurse cells to promote border cell migration. We are also assessing genetic interaction between the synthases and Pxt. We find that co-reduction of both Pxt and PGFS results in delayed border cell migration; supporting that the phenotype due to loss of PGFS is related to loss of PG signaling. Together our data lead to the model that PGE₂ and PGF_2α both promote on-time border cell migration. As PG signaling is highly conserved, these studies provide critical insight into the specific functions of individual PG signaling cascades controlling collective cell migration and can be applied to understanding both developmental collective cell migrations and pathological migrations including cancer metastasis.