title: Suppressed production of methyl farnesoid hormones yields developmental defects and lethality in Drosophila larvae.
abstract: A long-unresolved question in the developmental biology of Drosophila melanogaster has been whether methyl farnesoid hormones secreted by the ring gland are necessary for larval maturation and metamorphosis. In this study, we have used RNAi techniques to inhibit 3-Hydroxy-3-Methylglutaryl CoA Reductase (HMGCR) expression selectively in the corpora allatal cells that produce the circulating farnesoid hormones. The developing larvae manifest a number of developmental, metabolic and morphogenetic derangements. These defects included the exhibition of an "ultraspiracle" death phenotype at the 1st to 2nd instar larval molt, similar to that exhibited by animals that are null for the farnesoid receptor ultraspiracle. The few larvae surviving past a second lethal period at the 2nd to 3rd instar larval molt, again with "ultraspiracle" phenotype, often became developmentally arrested after either attaining a misformed puparium or after formation of the white pupa. Survival past the "ultraspiracle" lethal phenotype could be rescued by dietary provision of an endogenous dedicated precursor to the three naturally secreted methyl farnesoid hormones. In addition to these developmental and morphogenetic defects, most larvae that survived to the late second instar exhibited a posterior-originating melanization of the tracheal system. These results support the hypothesis that larval methyl farnesoid hormones are necessary for larval survival and morphogenetic transformation through the larval and pupal metamorphic processes.
authors: Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40506, USA. djones@uky.edu
authors: Davy
authors: D
authors: Jones
authors: Grace
authors: G
authors: Jones
authors: Peter
authors: P
authors: Teal
authors: Courey
authors: C
authors: Hammac
authors: Lexa
authors: L
authors: Messmer
authors: Kara
authors: K
authors: Osborne
authors: Yasser Hadj
authors: YH
authors: Belgacem
authors: Jean-Rene
authors: JR
authors: Martin
mesh_terms: D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis* / Q000378:metabolism*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D008675:Metamorphosis, Biological / Q000235:genetics / Q000502:physiology; D034622:RNA Interference
chemical_list: D029721:Drosophila Proteins; D005231:Fatty Acids, Unsaturated; C032429:methyl farnesoate; D006903:Hydroxymethylglutaryl CoA Reductases