title: Secretory competence in a gateway endocrine cell conferred by the nuclear receptor βFTZ-F1 enables stage-specific ecdysone responses throughout development in Drosophila.
abstract: Hormone-induced changes in gene expression initiate periodic molts and metamorphosis during insect development. Successful execution of these developmental steps depends upon successive phases of rising and falling 20-hydroxyecdysone (20E) levels, leading to a cascade of nuclear receptor-driven transcriptional activity that enables stage- and tissue-specific responses to the steroid. Among the cellular processes associated with declining steroids is acquisition of secretory competence in endocrine Inka cells, the source of ecdysis triggering hormones (ETHs). We show here that Inka cell secretory competence is conferred by the orphan nuclear receptor βFTZ-F1. Selective RNA silencing of βftz-f1 in Inka cells prevents ETH release, causing developmental arrest at all stages. Affected larvae display buttoned-up, the ETH-null phenotype characterized by double mouthparts, absence of ecdysis behaviors, and failure to shed the old cuticle. During the mid-prepupal period, individuals fail to translocate the air bubble, execute head eversion and elongate incipient wings and legs. Those that escape to the adult stage are defective in wing expansion and cuticle sclerotization. Failure to release ETH in βftz-f1 silenced animals is indicated by persistent ETH immunoreactivity in Inka cells. Arrested larvae are rescued by precisely-timed ETH injection or Inka cell-targeted βFTZ-F1 expression. Moreover, premature βftz-f1 expression in these cells also results in developmental arrest. The Inka cell therefore functions as a "gateway cell", whose secretion of ETH serves as a key downstream physiological output enabling stage-specific responses to 20E that are required to advance through critical developmental steps. This secretory function depends on transient and precisely timed βFTZ-F1 expression late in the molt as steroids decline.
authors.affiliation: Departments of Entomology and Cell Biology & Neuroscience, 2103 Biological Sciences Building, University of California, Riverside, CA 92521, USA.
authors.forename: Kook-Ho
authors.initials: KH
authors.lastname: Cho
authors.affiliation: Institute of Zoology, Slovak Academy of Sciences, Dubravska cesta 9, 84506 Bratislava, Slovakia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Daubnerová
authors.affiliation: Department of Entomology, 123 Waters Hall, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Yoonseong
authors.initials: Y
authors.lastname: Park
authors.affiliation: Institute of Zoology, Slovak Academy of Sciences, Dubravska cesta 9, 84506 Bratislava, Slovakia.
authors.forename: Dusan
authors.initials: D
authors.lastname: Zitnan
authors.affiliation: Departments of Entomology and Cell Biology & Neuroscience, 2103 Biological Sciences Building, University of California, Riverside, CA 92521, USA. Electronic address: michael.adams@ucr.edu.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Adams
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000254:growth & development* / Q000502:physiology; D004440:Ecdysone / Q000502:physiology*; D004702:Endocrine Glands / Q000166:cytology*; D055785:Gene Knockdown Techniques; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011987:Receptors, Steroid / Q000235:genetics / Q000502:physiology*
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D011987:Receptors, Steroid; C080885:nuclear hormone receptor FTZ-F1 beta, Drosophila; D004440:Ecdysone
keywords: DrmETH; Drosophila; Drosophila melanogaster ETH; EH; ETH; ETH-GeneSwitch; ETH-IR; ETHGS; Ecdysis; Ecdysis triggering hormone (ETH); Inka cells; RNA-silencing; Secretory competence; ecdysis triggering hormone; ecdysis triggering hormone-like immunoreactivity; eclosion hormone; βFTZ-F1