Affiliation: University of Maryland, Baltimore County
Keywords: p. cell migration; r. cell migration
Migratory cells play a significant role in spatiotemporally-regulated physiological processes such as normal embryonic development and wound healing. Dysregulation of these cells has severe implications in birth defects and diseases such as cancer. Border cell migration, during Drosophila oogenesis, serves as a useful model to study collective cell migration in vivo. Derived from the anterior epithelium of the egg chamber, the border cell cluster migrates toward the posteriorly-located oocyte in a temporally regulated manner. Developmental timing in flies is largely controlled by the sole steroid hormone ecdysone, which binds to a heterodimeric receptor complex that regulates transcription. Our work focuses on understanding how signaling by the ecdysone receptor (EcR), a conserved nuclear hormone receptor, affects border cell migration. Downregulation of ecdysone signaling results in delayed migration as a result of late detachment from the epithelium and slower migration. The directional translocation of the cluster, in response to chemoattractants, requires the extension of actin-rich protrusions that adhere to other cells in the migratory path. Live imaging video analysis revealed that clusters expressing transcriptionally-inactive EcR extend fewer functional protrusions. Protrusion stabilization, cluster integrity, and migration are contingent on optimal distribution of the adhesion molecule, E-cadherin. Immunofluorescence characterization of E-cadherin showed variations in the levels and localization in border cells with reduced ecdysone signaling. We hypothesize transcription by EcR is important for migration and could explain some of the above phenotypes. Thus, we are studying potential migratory roles of EcR targets. Additionally, we are assaying EcR binding sites within migration-specific target gene loci using bioinformatic and chromatin immunoprecipitation analyses. Interestingly, an EcR transcriptional reporter is specifically activated in the cluster despite the apparent availability of the signalling components throughout the egg chamber. We are investigating possible reasons for transcriptional specificity such as genetic interactions between chromatin regulators and EcR. Elucidating the role of EcR in cell migration kinetics will be a useful guide to improve our understanding of nuclear hormone receptors in development and disease.