title: Steroid signaling promotes stem cell maintenance in the Drosophila testis.
abstract: Stem cell regulation by local signals is intensely studied, but less is known about the effects of hormonal signals on stem cells. In Drosophila, the primary steroid twenty-hydroxyecdysone (20E) regulates ovarian germline stem cells (GSCs) but was considered dispensable for testis GSC maintenance. Male GSCs reside in a microenvironment (niche) generated by somatic hub cells and adjacent cyst stem cells (CySCs). Here, we show that depletion of 20E from adult males by overexpressing a dominant negative form of the Ecdysone receptor (EcR) or its heterodimeric partner ultraspiracle (usp) causes GSC and CySC loss that is rescued by 20E feeding, uncovering a requirement for 20E in stem cell maintenance. EcR and USP are expressed, activated and autonomously required in the CySC lineage to promote CySC maintenance, as are downstream genes ftz-f1 and E75. In contrast, GSCs non-autonomously require ecdysone signaling. Global inactivation of EcR increases cell death in the testis that is rescued by expression of EcR-B2 in the CySC lineage, indicating that ecdysone signaling supports stem cell viability primarily through a specific receptor isoform. Finally, EcR genetically interacts with the NURF chromatin-remodeling complex, which we previously showed maintains CySCs. Thus, although 20E levels are lower in males than females, ecdysone signaling acts through distinct cell types and effectors to ensure both ovarian and testis stem cell maintenance.
authors.affiliation: Department of Cell Biology, 725 N. Wolfe Street, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cell Biology, 725 N. Wolfe Street, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Cell Biology, 725 N. Wolfe Street, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Cherry
authors.affiliation: Department of Cell Biology, 725 N. Wolfe Street, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: matunis@jhmi.edu.
authors.forename: Erika L
authors.initials: EL
authors.lastname: Matunis
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004330:Drosophila; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D004441:Ecdysterone / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells; D008297:Male; D020033:Protein Isoforms; D011987:Receptors, Steroid / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction; D013737:Testis; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C437989:E(bx) protein, Drosophila; D020033:Protein Isoforms; D011987:Receptors, Steroid; D014157:Transcription Factors; C066030:USP protein, Drosophila; C055469:ecdysone receptor; C499712:nuclear hormone receptor FTZ-F1, Drosophila; C061375:Eip75B protein, Drosophila; D004441:Ecdysterone
keywords: Drosophila spermatogenesis; Ecdysone; NURF; Stem cell niche
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