title: Nutrient-dependent expression of insulin-like peptides from neuroendocrine cells in the CNS contributes to growth regulation in Drosophila.
abstract: BACKGROUND
  The insulin/IGF-1 signaling pathway controls cellular and organismal growth in many multicellular organisms. In Drosophila, genetic defects in components of the insulin signaling pathway produce small flies that are delayed in development and possess fewer and smaller cells as well as female sterility, reminiscent of the phenotypes of starved flies.
  
  
  RESULTS
  Here we establish a causal link between nutrient availability and insulin-dependent growth. We show that in addition to the Drosophila insulin-like peptide 2 (dilp2) gene, overexpression of dilp1 and dilp3-7 is sufficient to promote growth. Three of the dilp genes are expressed in seven median neurosecretory cells (m-NSCs) in the brain. These m-NSCs possess axon terminals in the larval endocrine gland and on the aorta, from which DILPs may be released into the circulatory system. Although expressed in the same cells, the expression of the three genes is controlled by unrelated cis-regulatory elements. The expression of two of the three genes is regulated by nutrient availability. Genetic ablation of these neurosecretory cells mimics the phenotype of starved or insulin signaling mutant flies.
  
  
  CONCLUSIONS
  These results point to a conserved role of the neuroendocrine axis in growth control in multicellular organisms.
authors.affiliation: Zoologisches Institut, Universität Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland.
authors.forename: Tomoatsu
authors.initials: T
authors.lastname: Ikeya
authors.forename: Milos
authors.initials: M
authors.lastname: Galic
authors.forename: Priyanka
authors.initials: P
authors.lastname: Belawat
authors.forename: Knud
authors.initials: K
authors.lastname: Nairz
authors.forename: Ernst
authors.initials: E
authors.lastname: Hafen
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D004275:DNA, Ribosomal / Q000235:genetics; D004330:Drosophila / Q000254:growth & development* / Q000502:physiology; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins / Q000235:genetics*; D007328:Insulin / Q000502:physiology; D009420:Nervous System / Q000254:growth & development; D009490:Neurosecretory Systems / Q000166:cytology / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics
chemical_list: C111892:DIAP2 protein, Drosophila; D004275:DNA, Ribosomal; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D007328:Insulin; D020033:Protein Isoforms