Ras signaling modulates activity of the Ecdysone Receptor EcR during cell migration in the drosophila ovary

Ecdysone Receptor (EcR) mediates effects of the hormone ecdysone during larval molts, pupal metamorphosis, and adult female oogenesis. In the ovary, egg chamber formation requires interactions between the somatic follicle cell (FC) epithelium and the germ line nurse cell/oocyte cyst. Previous work has shown EcR is required in the germ line for egg chamber maturation, and here we examine EcR requirements in the FC at late stages of oogenesis. EcR protein is ubiquitous in the FC but its activity is restricted, visualized by activity of the "ligand sensor" hs-GAL4-EcR ligand binding domain fusion and EcRE-lacZ reporter gene expression. GAL4-EcR is activated in the FC by an ecdysone agonist and repressed by tissue-specific Ras GTPase signals. To determine the significance of restricted sites of EcR activity in the FC, we used targeted misexpression of the dominant negative EcR (EcR-DN) molecules EcR^F645A and EcR^W650A. EcR-DN expression at stage 10 reduced EcRE-lacZ expression in the nurse cell FC and resulted in abnormal FC migrations, including aberrant centripetal migration and dorsal appendage tube formation, leading to the formation of cup-shaped eggs with shortened, branched dorsal appendages at stage 14. Clones of FC expressing EcR-DN displayed cell-autonomous increases in DE-cadherin expression and abnormal epithelial junction formation. EcR-DN expression caused thin eggshell phenotypes that correlated with both reduced levels of chorion gene expression and reduction in chorion gene amplification. Our results indicate that tissue-specific modulation of EcR activity by the Ras signaling pathway refines temporal ecdysone signals that regulate FC differentiation and cadherin-mediated epithelial cell shape changes.