title: A Genetic Mosaic Screen Reveals Ecdysone-Responsive Genes Regulating Drosophila Oogenesis.
abstract: Multiple aspects of Drosophila oogenesis, including germline stem cell activity, germ cell differentiation, and follicle survival, are regulated by the steroid hormone ecdysone. While the transcriptional targets of ecdysone signaling during development have been studied extensively, targets in the ovary remain largely unknown. Early studies of salivary gland polytene chromosomes led to a model in which ecdysone stimulates a hierarchical transcriptional cascade, wherein a core group of ecdysone-sensitive transcription factors induce tissue-specific responses by activating secondary branches of transcriptional targets. More recently, genome-wide approaches have identified hundreds of putative ecdysone-responsive targets. Determining whether these putative targets represent bona fide targets in vivo, however, requires that they be tested via traditional mutant analysis in a cell-type specific fashion. To investigate the molecular mechanisms whereby ecdysone signaling regulates oogenesis, we used genetic mosaic analysis to screen putative ecdysone-responsive genes for novel roles in the control of the earliest steps of oogenesis. We identified a cohort of genes required for stem cell maintenance, stem and progenitor cell proliferation, and follicle encapsulation, growth, and survival. These genes encode transcription factors, chromatin modulators, and factors required for RNA transport, stability, and ribosome biogenesis, suggesting that ecdysone might control a wide range of molecular processes during oogenesis. Our results suggest that, although ecdysone target genes are known to have cell type-specific roles, many ecdysone response genes that control larval or pupal cell types at developmental transitions are used reiteratively in the adult ovary. These results provide novel insights into the molecular mechanisms by which ecdysone signaling controls oogenesis, laying new ground for future studies.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205 Division of Reproductive Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205 Department of Biology, East Carolina University, Greenville, North Carolina 27858 ablese@ecu.edu dbarbosa@jhu.edu.
authors.forename: Elizabeth T
authors.identifier: 0000-0002-6934-9302
authors.initials: ET
authors.lastname: Ables
authors.affiliation: Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205 Division of Reproductive Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205.
authors.forename: Grace H
authors.initials: GH
authors.lastname: Hwang
authors.affiliation: Department of Biology, East Carolina University, Greenville, North Carolina 27858.
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Finger
authors.affiliation: Department of Biology, East Carolina University, Greenville, North Carolina 27858.
authors.forename: Taylor D
authors.initials: TD
authors.lastname: Hinnant
authors.affiliation: Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205 Division of Reproductive Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205 Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205 ablese@ecu.edu dbarbosa@jhu.edu.
authors.forename: Daniela
authors.initials: D
authors.lastname: Drummond-Barbosa
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019070:Cell Lineage; D002470:Cell Survival / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics*; D004440:Ecdysone / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005821:Genetic Techniques; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics; D007814:Larva / Q000187:drug effects / Q000235:genetics; D009030:Mosaicism; D009154:Mutation; D009866:Oogenesis / Q000187:drug effects / Q000235:genetics*; D010053:Ovary / Q000166:cytology / Q000502:physiology*; D011679:Pupa / Q000235:genetics; D011987:Receptors, Steroid / Q000235:genetics; D013234:Stem Cells / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C487427:Hrb27C protein, Drosophila; D011987:Receptors, Steroid; C080885:nuclear hormone receptor FTZ-F1 beta, Drosophila; C405957:tetratricopeptide repeat protein 2, Drosophila; D004440:Ecdysone
keywords: follicle cells; germline; nuclear hormone receptor; stem cells; steroid hormone