Comprehensive analyses of causative genes for intellectual disability and autism-spectrum disorders

• Project/Area Number: 24390271
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Institute for Developmental Research, Aichi Human Service Center
• Principal Investigator: Nagata Koh-ichi 愛知県心身障害者コロニー発達障害研究所, 神経制御学部, 部長 (50252143)
• Co-Investigator(Kenkyū-buntansha): 山形 崇倫 自治医科大学, 医学部, 教授 (00239857) ; 原 明 岐阜大学, 医学(系)研究科(研究院), 教授 (10242728)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 自閉性障害 / 知的障害 / 大脳皮質構築 / 神経細胞 / 自閉性疾患 / 大脳皮質 / 大脳皮質発生 / セプチン

Outline of Final Research Achievements

While many different biological causes have been implicated in the etiologies of neurodevelopmental disorders such as autism-spectrum disorder (ASD) and intellectual disability (ID), genetic factors are considered to be the most important. Thus, it is essential to clarify the pathophysiological significance of respective disease-related genes in brain development. To address this issue, we have established a battery of in utero electroporation-based ex vivo and in vitro observations including cortical neuron migration, axon elongation, dendrite development, spine morphogenesis and live-imaging as well as cell biological and biochemical analyses.

Research Products

• [Int'l Joint Research] Pohang University(韓国)
• [Int'l Joint Research] Duke-National University of Singapore(Singapore)
• [Int'l Joint Research] Pohang University(韓国)
• [Int'l Joint Research] Duke-National University of Singapore(Singapore)
• [Journal Article] Role of the cytoplasmic isoform of RBFOX1/A2BP1 in establishing the architecture of the developing cerebral cortex. (2015)
  • Author(s): Hamada N, Ito H, Iwamoto I, Morishita R, Tabata H, Nagata K-I
  • Journal Title: Molecular Autism Volume: 6 Issue: 1 Pages: 56-56
  • DOI: 10.1186/s13229-015-0049-5
  • Peer Reviewed / Open Access
• [Journal Article] Disrupted-in-schizophrenia 1 (DISC1) regulates dysbindin function by enhancing its stability. (2015)
  • Author(s): Lee S-A, Kim S-M, Suh B K, Sun H-Y, Park Y-U, Hong J-H, Park C, Nguyen M D, Nagata K, Yoo J-Y, Park S K
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 11 Pages: 7087-7096
  • DOI: 10.1074/jbc.m114.614750
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Role of an adaptor protein Lin-7B in brain development: possible involvement in autism spectrum disorders. (2015)
  • Author(s): Mizuno M, Matsumoto A, Hamada N, Ito H, Miyauchi A, Jimbo EF, Momoi MY, Tabata H, Yamagata T, Nagata K.
  • Journal Title: J Neurochem Volume: 132 Issue: 1 Pages: 61-69
  • DOI: 10.1111/jnc.12943
  • Peer Reviewed / Open Access
• [Journal Article] Morphological characterization of mammalian Timeless in the mouse brain development. (2015)
  • Author(s): Inaguma Y, Ito H, Hara A, Iwamoto I, Matsumoto A, Yamagata T, Tabata H, Nagata K.
  • Journal Title: Neurosci Res Volume: 92 Pages: 21-28
  • DOI: 10.1016/j.neures.2014.10.017
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Expression of Drebrin, an actin binding protein, in basal cell carcinoma, trichoblastoma and trichoepithelioma. (2014)
  • Author(s): Mizutani Y, Iwamoto I, Kanoh H, Seishima M and Nagata K.
  • Journal Title: Histol Histopathol Volume: 29 Pages: 757-766
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] SIL1, a causative cochaperone gene of Marinesco-Sjogren syndrome, plays an essential role in establishing the architecture of the developing cerebral cortex. (2014)
  • Author(s): Hamada N, Inaguma Y, Tabata H, Iwamoto I, Mizuno M, Nishimura YV, Ito H, Morishita R, Suzuki M, Ohno K, Kumagai T, Nagata K.
  • Journal Title: EMBO Mol Med. Volume: 6 Issue: 3 Pages: 414-29
  • DOI: 10.1002/emmm.201303069
  • Peer Reviewed / Open Access
• [Journal Article] LIN7A depletion disrupts cerebral cortex development, contributing to intellectual disability in 12q21-deletion syndrome. (2014)
  • Author(s): Matsumoto A, Mizuno M, Hamada N, Nozaki Y, Jimbo E, Momoi M, Nagata K, Yamagata T
  • Journal Title: PLOS ONE Volume: 9 Issue: 3 Pages: e92695-e92695
  • DOI: 10.1371/journal.pone.0092695
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of an in vivo electroporation method into postnatal newborn neurons in the dentate gyrus. (2014)
  • Author(s): Ito H, Morishita R, Iwamoto I, Nagata K.
  • Journal Title: Hippocampus Volume: 24 Issue: 12 Pages: 1449-1457
  • DOI: 10.1002/hipo.22325
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cell biological characterization of a multidomain adaptor protein, ArgBP2, in epithelial NMuMG cells, and identification of a novel short isoform. (2012)
  • Author(s): Murase K, Ito H, Kanoh H, Sudo K, Iwamoto I, Morishita R, Soubeyran P, Seishima M, Nagata K.
  • Journal Title: Med Mol Morphol. Volume: 45 Issue: 1 Pages: 22-28
  • DOI: 10.1007/s00795-010-0537-9
  • NAID: 10030573597
  • Peer Reviewed
• [Journal Article] Biochemical and morphological characterization of MAGI-1 in neuronal tissue. (2012)
  • Author(s): Ito H, Morishita R, Sudo K, Nishimura YV, Inaguma Y, Iwamoto I, Nagata KI.
  • Journal Title: J Neurosci Res Volume: 90 Issue: 9 Pages: 1776-1781
  • DOI: 10.1002/jnr.23074
  • Peer Reviewed
• [Presentation] Comprehensive approach to understand pathophysiological role of SIL1, a gene causing intellectual disability. (2015)
  • Author(s): Nagata K
  • Organizer: 25th Meeting of International Society for Neurochemistry
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2015-08-23
  • Int'l Joint Research / Invited
• [Presentation] Comprehensive approach with an analytical battery to understand pathophysiological role of A2BP1/RBFOX1, a "hub" gene in the ASD gene transcriptome network (2015)
  • Author(s): Koh-ichi Nagata
  • Organizer: Keystone Symposia on Molecular and Cellular Biology
  • Place of Presentation: Tahoe City, California, USA
  • Year and Date: 2015-03-16 – 2015-03-20
  • Invited
• [Presentation] Comprehensive approach with an analytical battery to understand pathophysiological role of A2BP1/RBFOX1, a "hub" gene in the ASD gene transcriptome network (2015)
  • Author(s): Hamada N, Ito H, Tabata H, Nagata K
  • Organizer: Keystone Symposia on Molecular and Cellular BiologyPathways of Neurodevelopmental Disorders
  • Place of Presentation: Tahoe City, California, USA
  • Year and Date: 2015-03-16
  • Int'l Joint Research / Invited
• [Presentation] 自閉症スペクトラム障害の病態関連遺伝子の機能解析 (2014)
  • Author(s): 永田浩一
  • Organizer: 第56回日本小児神経学会学術集会シンポジウム
  • Place of Presentation: 浜松
  • Year and Date: 2014-05-29 – 2015-05-31
  • Invited
• [Presentation] Symposium "Molecular basis of schizophrenia: From the susceptibility genes"Analyses of a schizophrenia susceptibility gene product, Dysbindin, in spine morphogenesis. (2012)
  • Author(s): Nagata, K, Ito, H.
  • Organizer: The 11th Biennial Joint Meeting of APSN & JSN
  • Place of Presentation: 神戸国際会議場(Kobe)(招待講演)
  • Year and Date: 2012-10-02
• [Presentation] シンポジウム小児神経の「臨床」における「分子・形態」アプローチ;マリネスコ・シェーグレン症候群の原因遺伝子SIL1の分子形態学的解析 (2012)
  • Author(s): 永田浩一
  • Organizer: 第44回日本臨床分子形態学会総会
  • Place of Presentation: 高知市文化プラザ(高知)(招待講演)