Steroid hormone signaling activity modulates cell migration kinetics in Drosophila through transcriptional and post-transcriptional mechanisms

dc.contributor.advisorStarz-Gaiano, Michelle
dc.contributor.authorBhattacharya, Mallika
dc.contributor.departmentBiological Sciences
dc.contributor.programBiological Sciences
dc.description.abstractCollective cell migration is indispensable to spatiotemporally-regulated biological events such as embryonic development, immune response, and wound healing. Dysregulation of cell motility has severe implications in birth defects and diseases such as metastatic cancers. Border cell migration, during Drosophila oogenesis, is an effective, genetically tractable model system to study collective cell migration in vivo. Reduced gene redundancy in Drosophila is advantageous as it narrows the focus to critical regulators. Derived from a somatic epithelium, the border cell cluster is a cohesive group that migrates toward the oocyte. The directional translocation of the cluster, in response to chemoattractants, is temporally regulated and requires the extension of actin-rich protrusions that adhere to other cells in the migratory path. Ecdysone, the sole steroid hormone in flies, controls the timing of developmental progression. It regulates transcription by binding to a highly conserved heterodimeric receptor complex made of Ecdysone Receptor (EcR) and Ultraspiracle. Blocking EcR-mediated transcriptional activity disrupts migration, but the mechanisms involved are not well understood. By blocking ecdysone signaling, we show that the incomplete migration phenotype results from a combination of delayed detachment and slower migration. Live imaging and immunofluorescence analysis revealed that clusters expressing a transcriptionally-inactive, dominant negative isoform of EcR have defects in protrusion dynamics and aberrant spatial distributions of E-cadherin, Discs large, and activated myosin; all three of which have established roles in migration mechanics. As these proteins do not appear to be direct transcriptional targets, we propose that they are regulated post-transcriptionally through other EcR transcriptional targets. We also investigate the high EcR transcriptional activity specific to border cells in multiple ways. Using a genetic screen with an EcR mutant, we identify interactions with chromatin remodelers domino and brahma, which may act to reorganize chromatin at targets to trigger migration. Additionally, we bioinformatically assay for EcR binding sites within border cell-specific, EcR target loci, and test the requirement for two EcR targets in migration. Lastly, we investigate the contributions of the putative E3 ubiquitin ligase Mind bomb 2 to migration. Overall, this research advances our understanding of transcriptional and post-transcriptional mechanisms by which steroid hormone signaling regulates migration.
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Biological Sciences Department Collection
dc.relation.ispartofUMBC Theses and Dissertations Collection
dc.relation.ispartofUMBC Graduate School Collection
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dc.sourceOriginal File Name: Bhattacharya_umbc_0434D_12736.pdf
dc.subjectCell migration
dc.subjectDrosophila melanogaster
dc.subjectSteroid hormone
dc.titleSteroid hormone signaling activity modulates cell migration kinetics in Drosophila through transcriptional and post-transcriptional mechanisms
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