title: Local requirement of the Drosophila insulin binding protein imp-L2 in coordinating developmental progression with nutritional conditions.
abstract: In Drosophila, growth takes place during the larval stages until the formation of the pupa. Starvation delays pupariation to allow prolonged feeding, ensuring that the animal reaches an appropriate size to form a fertile adult. Pupariation is induced by a peak of the steroid hormone ecdysone produced by the prothoracic gland (PG) after larvae have reached a certain body mass. Local downregulation of the insulin/insulin-like growth factor signaling (IIS) activity in the PG interferes with ecdysone production, indicating that IIS activity in the PG couples the nutritional state to development. However, the underlying mechanism is not well understood. In this study we show that the secreted Imaginal morphogenesis protein-Late 2 (Imp-L2), a growth inhibitor in Drosophila, is involved in this process. Imp-L2 inhibits the activity of the Drosophila insulin-like peptides by direct binding and is expressed by specific cells in the brain, the ring gland, the gut and the fat body. We demonstrate that Imp-L2 is required to regulate and adapt developmental timing to nutritional conditions by regulating IIS activity in the PG. Increasing Imp-L2 expression at its endogenous sites using an Imp-L2-Gal4 driver delays pupariation, while Imp-L2 mutants exhibit a slight acceleration of development. These effects are strongly enhanced by starvation and are accompanied by massive alterations of ecdysone production resulting most likely from increased Imp-L2 production by neurons directly contacting the PG and not from elevated Imp-L2 levels in the hemolymph. Taken together our results suggest that Imp-L2-expressing neurons sense the nutritional state of Drosophila larvae and coordinate dietary information and ecdysone production to adjust developmental timing under starvation conditions.
authors.affiliation: Institute for Molecular Systems Biology (IMSB), ETH Zurich, Zurich 8093, Switzerland. sarrafzadeh@imsb.biol.ethz.ch
authors.forename: Ladan
authors.initials: L
authors.lastname: Sarraf-Zadeh
authors.forename: Stefan
authors.initials: S
authors.lastname: Christen
authors.forename: Uwe
authors.initials: U
authors.lastname: Sauer
authors.forename: Paola
authors.initials: P
authors.lastname: Cognigni
authors.forename: Irene
authors.initials: I
authors.lastname: Miguel-Aliaga
authors.forename: Hugo
authors.initials: H
authors.lastname: Stocker
authors.forename: Katja
authors.initials: K
authors.lastname: Köhler
authors.forename: Ernst
authors.initials: E
authors.lastname: Hafen
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000254:growth & development*; D004440:Ecdysone / Q000378:metabolism; D004441:Ecdysterone / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007814:Larva / Q000254:growth & development; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D020033:Protein Isoforms; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D019076:Transgenes
chemical_list: D029721:Drosophila Proteins; C557617:GAL4 protein, Drosophila; C498778:Imp protein, Drosophila; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D004440:Ecdysone; D004441:Ecdysterone
keywords: 20-hydroxyecdysone; 20E; AED; CC; Dilp; Drosophila; Drosophila insulin-like peptide; Ecdysone; IGF; IGFBP; IIS; IPC; Imaginal morphogenesis factor-Late2; Imaginal morphogenesis protein-Late 2; Imp-L2; InR; LOF; NPF; Neuron; PG; PTTH; Prothoracic Gland; SOG; TOR; Target of Rapamycin; after egg deposition; corpora cardiac; insulin producing cells; insulin receptor; insulin-like growth factor binding proteins; insulin-like growth factors; insulin/insulin-like growth factor signaling; loss of function; neuropeptide F; prothoracic gland; prothoracicotrophic hormone; subesophageal ganglion