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2005 Fiscal Year Final Research Report Summary

Molecular characterizations of the Drosophila homolog of the fragile X gene FMR1 in neuronal morphology and function

Research Project

Project/Area Number 15207002
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Genetics/Genome dynamics
Research InstitutionThe University of Tokushima

Principal Investigator

SIOMI Haruhiko  The University of Tokushima, Institute for Genome Research, Professor, ゲノム機能研究センター, 教授 (60202107)

Co-Investigator(Kenkyū-buntansha) SAITOE Minoru  Tokyo Metropolitan Institute for Neuroscience, Group leader, 東京都神経科学総合研究所, 主任研究員 (50261839)
ISHIDA Norio  National Institute of Advanced Industrial Science and Technology, Institute for Biological Resources and Functions, Group leader, 生物機能工学研究部門, グループ長 (00344234)
Project Period (FY) 2003 – 2005
Keywordsfragile X syndrome / FMR1 / Drosophila / olfactory learning and memory / neuro-muscular junction (NMJ) / circadian rhythms / RNAi
Research Abstract

Fragile X syndrome is a common form of inherited mental retardation caused by the loss of FMR1 expression. The FMR1 gene encodes an RNA-binding protein that associates with translating ribosomes and acts as a translational repressor. Our previous work on the Drosophila homolog of FMR1 gene, dFMR1,showed that dFMR1 interacts with RNAi-related molecules, such as AGO2 and small RNA (Ishizuka et al.2002). Recently we showed that dFMR1-associated complexes also contain a courtship regulator Lingerer (Lig). Consistently, dFMR1 and Lig are co-expressed in the nervous system. We found that Lig hypomorphs display shrunken synaptic terminals at the neuromuscular junction in third instar larvae, whereas in dFMR1 mutant synaptic terminals were expanded. Genetic interaction between the two genes was implicated because dFMR1/Lig double mutants restore normal synaptic structure.
We also demonstrated that dFMR1 flies exhibit defects in olfactory memory. Short-term memory, but not long-term memory, is impaired in dFMR1 flies. In addition, we were able to show that the observed deficits in circadian locomotor activity in dFMR1 flies can be rescued by an introduction of the human FMR1 gene as a trans gene.
Further characterization of dFMR1-Lingerer-AGO2 interaction should help us to understand translational regulation by dFMR1 and thereby the molecular mechanisms that cause the fragile X syndrome.

  • Research Products

    (50 results)

All 2006 2005 2004 2003 2002

All Journal Article (48 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Adrenal gland-dependent augmentation of plasminogen activator inhibitor-1 (PAI-1) expression in streptozotocin-induced diabetic mice.2006

    • Author(s)
      Oishi K
    • Journal Title

      JOURNAL OF THROMBOSIS AND HAEMOSTASIS (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Clock mutant mice with Jcl/ICR background shows an impaired learning ability in water maze, but not in passive avoidance, at the beginning of dark phase.2006

    • Author(s)
      Sei H
    • Journal Title

      CONGENITAL ANOMALIES (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mating rhythms of Drosophlila : rescue of tim01mutants by D. ananassae timeless.2006

    • Author(s)
      Nishinokubi I
    • Journal Title

      Journal of Circadian Ryhthms 44

      Pages: 1-13

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73.2006

    • Author(s)
      Hoshino M
    • Journal Title

      Cell Biol 172

      Pages: 589-604

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] In vitro pre-miRNA processing assays using Drosophila S2 cell lysates.2006

    • Author(s)
      Ishizuka, A.
    • Journal Title

      Methods in Molecular Biology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73.2006

    • Author(s)
      Hoshino M.
    • Journal Title

      J Cell Biol. 172

      Pages: 589-604

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mating rhythms of Drosophila : rescue of tim01mutants by D.ananassae timeless.2006

    • Author(s)
      Nishinokubi I.
    • Journal Title

      Journal of Circadian Rhythms 44

      Pages: 1-13

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells.2005

    • Author(s)
      Saito, K
    • Journal Title

      PLoS Biology 3(7)

      Pages: E235

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A potential link between transgene silencing and poly(A) tail.2005

    • Author(s)
      Siomi, MC
    • Journal Title

      RNA 11

      Pages: 1004-1011

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification of components of RNAi pathways using the Tandem Affinity Purification (TAP) method.2005

    • Author(s)
      Siomi, MC
    • Journal Title

      Methods in Molecular Biology 309

      Pages: 1-9

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Slicer function of Drosophlila Argonautes and its involvement in RISC formation.2005

    • Author(s)
      Miyoshi, K
    • Journal Title

      Genes & Development 19

      Pages: 2837-2848

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Differential circadian expression of Endothelin-1 mRNA in the rat suprachiasmatic nucleus and peripheral tissues.2005

    • Author(s)
      Hanai S
    • Journal Title

      NEUROSCIENCE LETTERS 377(1)

      Pages: 65-68

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] CLOCK is involved in the circadian transactivation of peroxisome proliferator-activated receptor a (PPARa) in mice.2005

    • Author(s)
      Oishi K
    • Journal Title

      BIOCHEMICAL JOURNAL 386

      Pages: 575-581

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Per2 gene expressions in the suprachiasmatic nucleus and liver differentially respond to nutritional factors in rats.2005

    • Author(s)
      Iwanaga H
    • Journal Title

      JOURNAL OF PARENTERAL AND ENTERAL NUTRITION 3

      Pages: 157-161

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Involvement of circadian clock gene Clock in diabetes-induced circadian augmentation of plasminogen activator inhibitor-1 (PAI-1) expression in the mouse heart.2005

    • Author(s)
      Oishi K
    • Journal Title

      FEBS LETTERS 579

      Pages: 3555-3559

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A role for glycogen synthase kinase-3 in the mammalian circadian clock.2005

    • Author(s)
      Iidaka C
    • Journal Title

      J. Biol Chem 280(33)

      Pages: 29397-29402

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Genome-wide expression analysis reveals 100 adrenal gland-dependent circadian genes in the mouse liver.2005

    • Author(s)
      Oishi K
    • Journal Title

      DNA RESEARCH 12(3)

      Pages: 191-202

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Disrupted fat absorption attenuates obesity induced by a high-fat diet in Clock mutant mice.2005

    • Author(s)
      Oishi K
    • Journal Title

      FEBS LETTERS 579

      Pages: 3555-3559

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Circadian expression of clock genes is maintained in the liver of vitamin A-deficient mice.2005

    • Author(s)
      Shirai H
    • Journal Title

      NEUROSCIENCE LETTERS (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Drosophila as a novel animal model for studying the genetics of age-related memory impairment.2005

    • Author(s)
      Saitoe M
    • Journal Title

      Rev Neurosci 16

      Pages: 137-149

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] NMDA receptors mediate olfactory learning and memory in Drosophila.2005

    • Author(s)
      Xia S_*, Miyashita T_*, Fu T-G_*
    • Journal Title

      Current Biology 15

      Pages: 603-615

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Can flies shed light on our own age-related memory impairment?2005

    • Author(s)
      Horiuchi J
    • Journal Title

      4

      Pages: 83-101

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells.2005

    • Author(s)
      Saito, K.
    • Journal Title

      PLoS Biology s(7)

      Pages: e235

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A potential link between transgene silencing and poly(A) tail2005

    • Author(s)
      Siomi, MC.
    • Journal Title

      RNA 11

      Pages: 1004-1011

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Slicer function of Drosophila Argonautes and its involvement in RISC formation2005

    • Author(s)
      Miyoshi, K.
    • Journal Title

      Genes & Development 19

      Pages: 2837-2848

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of components of RNAi pathways using the Tandem Affinity Purification (TAP) method.2005

    • Author(s)
      Siomi, MC.
    • Journal Title

      Methods in Molecular Biology 309

      Pages: 1-9

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Drosophila as a novel animal model for studying the genetics of age-related memory impairment.2005

    • Author(s)
      Saitoe M.
    • Journal Title

      Rev Neurosci 16

      Pages: 137-149

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] NMDA receptors mediate olfactory learning and memory in Drosophila.2005

    • Author(s)
      Xia S.
    • Journal Title

      Current Biology 15

      Pages: 603-615

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Can flies shed light on our own age-related memory impairment?2005

    • Author(s)
      Horiuchi J.
    • Journal Title

      Ageing Res Rev 4

      Pages: 83-101

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A role for glycogen synthase kinase-3 in the mammalian circadian clock.2005

    • Author(s)
      Iidaka C.
    • Journal Title

      Journal of Biological Chemistry 280

      Pages: 29397-29402

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways.2004

    • Author(s)
      Okamura, K
    • Journal Title

      Genes & Development 18

      Pages: 1655-1666

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] RNA Interference : A New Mechanism by Which FMRP Acts in the Normal Brain? - What can Drosophila teach us?2004

    • Author(s)
      Siomi, H
    • Journal Title

      MRDDR review 10

      Pages: 68-74

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Circadian Degradation of Clock Protein PER1 Regulated by Its Phosphorylation in Human Normal Fibroblasts.2004

    • Author(s)
      Miyazaki K
    • Journal Title

      BIOCHEMICAL JOURNAL 380(1)

      Pages: 95-103

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Gene-and tissue-specific alterations of circadian clock gene expression in streptozotocin-induced diabetic mice under restricted feeding,2004

    • Author(s)
      Oishi K
    • Journal Title

      BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATION 317

      Pages: 330-334

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effect of feeding on peripheral circadian rhythms and behaviour in mammals,2004

    • Author(s)
      Kobayashi H
    • Journal Title

      Genes to Cells 9

      Pages: 857-864

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The involvement of Cry1 and Cry2 genes in the regulation of the circadian body temperature rhythm in mice.2004

    • Author(s)
      Nagashima K
    • Journal Title

      AM J PHYSIOL-REG I

      Pages: 395

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Tissue-specific augmentation of circadian PAI-1 expression in mice with streptozotocin-induced diabetes.2004

    • Author(s)
      Oishi K
    • Journal Title

      THROMBOSIS RESEARCH 114

      Pages: 129-135

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] RNA Interference : A New Mechanism by Which FMRP Acts in the Normal Brain? -What can Drosophila teach us? -2004

    • Author(s)
      Siomi, H.
    • Journal Title

      MRDDR review 10

      Pages: 68-74

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effect of feeding on peripheral circadian rhythms and behaviour in mammals.2004

    • Author(s)
      Kobayashi H.
    • Journal Title

      Genes to Cells 9

      Pages: 857-864

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Increase of hippocampal acetylcholine release at the onset of dark phase is suppressed in a mutant mice model of evening-type individuals.2003

    • Author(s)
      Sei, H
    • Journal Title

      Neuroscience 117

      Pages: 785-789

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Protein Tyrosine Phosphatase PTP20 Induces Actin Cytoskeleton Reorganization by Dephosphorylating p190 RhoGAP in Rat Ovarian Granulosa Cells Stimulated with Follicle-Stimulating Hormone,2003

    • Author(s)
      Shiota M
    • Journal Title

      Biochem Biophys Res Commun 17(4)

      Pages: 534-549

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sex difference in circadian period of body temperature in Clock mutant mice with Jcl/ICR bachground.2003

    • Author(s)
      Ochi M
    • Journal Title

      Neuroscience Letters 347

      Pages: 163-166

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Bimodal circadian expression of serotonin N-actyltransferase mRNA in the retina of rats under restricted.2003

    • Author(s)
      Oishi K
    • Journal Title

      Neuroscience Letters

      Pages: 35121-35124

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Highly conserved Drosophila melanogaster.2003

    • Author(s)
      Nishinokubi I
    • Journal Title

      GENE

      Pages: 1-8

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Genome-wide expression analysis of mouse liver reveals CLOCK-regulated circadian output genes.2003

    • Author(s)
      Oishi K
    • Journal Title

      Jounal of Biological Chemistry 278

      Pages: 41519-41527

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Feeding is not a more potent Zeitgeber than the light-dark cycle in Drosophlila.2003

    • Author(s)
      Oishi K
    • Journal Title

      NeuroReport 15(4)

      Pages: 739-743

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Aging specifically impairs amnesiac-dependent memory in Drosophila.2003

    • Author(s)
      Tamura T
    • Journal Title

      40

      Pages: 1003-1011

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Genome-wide expression analysis of mouse liver reveals CLOCK-regulated circadian output genes.2003

    • Author(s)
      Oishi K.
    • Journal Title

      Journal of Biological Chemistry 278

      Pages: 41519-41527

    • Description
      「研究成果報告書概要(欧文)」より
  • [Patent(Industrial Property Rights)] 老人性記憶障害モデル非ヒト哺乳類及び非哺乳類動物2003

    • Inventor(s)
      齊藤実
    • Industrial Property Rights Holder
      東京都神経科学総合研究所
    • Industrial Property Number
      特願・2003-402319
    • Filing Date
      2003-12-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] ショウジョウバエを用いたヒト脆弱Xシンドローム治療薬候補化合物のスクリーニング方法2002

    • Inventor(s)
      霜田政美
    • Industrial Property Rights Holder
      産業技術総合研究所
    • Industrial Property Number
      特願・2002-321833
    • Filing Date
      2002-07-26
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2007-12-13  

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