title: A critical role for the Drosophila dopamine D1-like receptor Dop1R2 at the onset of metamorphosis.
abstract: Insect metamorphosis relies on temporal and spatial cues that are precisely controlled. Previous studies in Drosophila have shown that untimely activation of genes that are essential to metamorphosis results in growth defects, developmental delay and death. Multiple factors exist that safeguard these genes against dysregulated expression. The list of identified negative regulators that play such a role in Drosophila development continues to expand.
  
  
  
  By using RNAi transgene-induced gene silencing coupled to spatio/temporal assessment, we have unraveled an important role for the Drosophila dopamine 1-like receptor, Dop1R2, in development. We show that Dop1R2 knockdown leads to pre-adult lethality. In adults that escape death, abnormal wing expansion and/or melanization defects occur. Furthermore we show that salivary gland expression of this GPCR during the late larval/prepupal stage is essential for the flies to survive through adulthood. In addition to RNAi-induced effects, treatment of larvae with the high affinity D1-like receptor antagonist flupenthixol, also results in developmental arrest, and in morphological defects comparable to those seen in Dop1R2 RNAi flies. To examine the basis for pupal lethality in Dop1R2 RNAi flies, we carried out transcriptome analysis. These studies revealed up-regulation of genes that respond to ecdysone, regulate morphogenesis and/or modulate defense/immunity.
  
  
  
  Taken together our findings suggest a role for Dop1R2 in the repression of genes that coordinate metamorphosis. Premature release of this inhibition is not tolerated by the developing fly.
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, 02467, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Regna
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA, 02111, USA.|Present Address: Department of Biology, Stanford University, California, 94305, USA.
authors.forename: Peri T
authors.initials: PT
authors.lastname: Kurshan
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA, 02111, USA.
authors.forename: Benjamin N
authors.initials: BN
authors.lastname: Harwood
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, 02467, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Jenkins
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, 02111, USA.
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, 02467, USA.|Discovery Research, Biogen Idec, Cambridge, MA, 02142, USA.
authors.forename: Marc A T
authors.initials: MA
authors.lastname: Muskavitch
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA, 02111, USA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Kopin
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA, 02111, USA. idraper@tuftsmedicalcenter.org.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Draper
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000235:genetics / Q000254:growth & development; D008675:Metamorphosis, Biological / Q000235:genetics*; D011679:Pupa / Q000235:genetics / Q000254:growth & development; D034622:RNA Interference; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C000622444:Dop1R2 protein, Drosophila; D029721:Drosophila Proteins; D017447:Receptors, Dopamine D1
keywords: Development; Dopamine; GPCR; RNAi; Transcriptome