Functional analysis of CTCF for generating neuronal diversity and neuronal networks

• Project/Area Number: 24700410
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Fusional basic brain science
• Research Institution: Osaka University
• Principal Investigator: HIRAYAMA Teruyoshi 大阪大学, 生命機能研究科, 特任助教 (40437398)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: CTCF / Neuron / diversity / Protocadherin

Research Abstract

I generated postmitotic neurons specific CTCF conditional knockout mice and investigated the role of the brain and the regulation of clustered Pcdh genes. The CTCF-cKO mice exhibited growth retardation, abnormal behavior, and died within one month. Gene expression profile exhibited significant downregulation of clustered Protocadherin genes. I examined structure of somatosensory cortex and found that barrel structure was disappeared in the CTCF-cKO mice. I also found that the CTCF deficiency lead to morphological changes of dendrite and spine formation during neuronal maturation. These results indicate that CTCF is required for the refinement of somatosensory maps and stochastic expression of clustered Pcdh genes in neurons.

Research Products

• [Journal Article] Developmental epigenetic modification regulates stochastic expression of clustered protocadherin genes, generating single neuron diversity. (2014)
  • Author(s): Toyoda S, Kawaguchi M, Kobayashi T, Tarusawa E, Toyama T, Okano M, Oda M, Nakauchi H, Yoshimura Y, Sanbo M, Hirabayashi M, Hirayama T, Hirabayashi T, Yagi T.
  • Journal Title: Neuron Volume: 82 Issue: 1 Pages: 94-108
  • DOI: 10.1016/j.neuron.2014.02.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clustered Protocadherins and Neuronal Diversity (2013)
  • Author(s): Hirayama T. and Yagi T.
  • Journal Title: Progress in Molecular Biology and Translational Science Volume: Vol. 116 Pages: 145-167
  • DOI: 10.1016/b978-0-12-394311-8.00007-8
  • ISBN: 9780123943118
  • Peer Reviewed
• [Journal Article] CTCF is required for neural development and stochastic expression of clustered Pcdhgenes in neurons. (2012)
  • Author(s): Hirayama T, Yagi T.
  • Journal Title: Cell Reports Volume: 2 Issue: 2 Pages: 345-357
  • DOI: 10.1016/j.celrep.2012.06.014
  • Peer Reviewed
• [Presentation] CTCF is required for the refinement of somatosensory maps and stochastic expression of clustered Pcdh genes in neurons (2013)
  • Author(s): Hirayama T, Tarusawa E, Yoshimura Y, Galjart N, Yagi T
  • Organizer: EMBO meeting 2013
  • Place of Presentation: Amsterdam (Netherlands)
• [Presentation] Behavior analysis of CTCF-deficient mice specifically in Purkinje cell (2013)
  • Author(s): 角岡佑紀、平山晃斉、崎村建司、八木健
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Dnmt3b依存的なDNAメチル化は単一神経細胞におけるクラスター型プロトカドヘリン遺伝子群の確率的発現と樹状突起の自己忌避を制御する (2013)
  • Author(s): 豊田峻輔、川口将史、小林俊寛、足澤悦子、遠山知子、岡野正樹、小田昌朗、中内啓光、吉村由美子、三宝誠、平林真澄、平山晃斉、平林敬浩、八木健
  • Organizer: 第36回日本神経科学学会
  • Place of Presentation: 京都
• [Presentation] DNAポリメラーゼβの神経前駆体細胞における作用が大脳皮質における神経細胞分化に必要である (2013)
  • Author(s): 大西公平、菅生紀之、豊田峻輔、平山晃斉、八木健、山本亘彦
  • Organizer: 第36回日本神経科学学会
  • Place of Presentation: 京都
• [Presentation] CTCFによる神経細胞の多様化と神経回路形成 (2013)
  • Author(s): 平山晃斉、足澤悦子、吉村由美子、Galjart N、八木健
  • Organizer: 第7回日本エピジェネティック研究会年会
  • Place of Presentation: 奈良
• [Presentation] CTCFによる神経細胞の多様化と神経回路形成 (2013)
  • Author(s): 平山晃斉、足澤悦子、吉村由美子、Galjart N、八木健
  • Organizer: 第７回日本エピジェネティック研究会年会
  • Place of Presentation: 奈良
• [Presentation] DNAポリメラーゼβの神経前駆体細胞における作用が大脳皮質における神経細胞分化に必要である (2013)
  • Author(s): 大西公平、菅生紀之、豊田峻輔、平山晃斉、八木 健、山本亘彦
  • Organizer: 第36回日本神経科学学会
  • Place of Presentation: 神戸
• [Presentation] CTCF is required for the refinement of somatosensory maps and stochastic expression of clustered Pcdh genes in neurons (2013)
  • Author(s): Hirayama T, Tarusawa E, Yoshimura Y, Galjart N, Yagi T.
  • Organizer: EMBO Meeting 2013
  • Place of Presentation: Amsterdam (Netherlands）
• [Presentation] Behavior analysis of CTCF-deficient mice specifically in Purkinje cell（プルキンエ細胞特異的CTCF減少マウスの行動解析） (2013)
  • Author(s): 角岡佑紀、平山晃斉、崎村建司、八木健
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] CTCF is required for neural development and stochastic expression of clustered Pcdh genes in neurons (2012)
  • Author(s): Hirayama T, Tarusawa E, Yoshimura Y, Galjart N, Yagi T
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 博多
• [Presentation] Promoter DNA methylation is dependent on gene cluster structure and regulates allocation of isoforms expression in each Protocadherin cluster (2012)
  • Author(s): Toyoda S, Kawaguchi M, Toyama T, Okano M, Oda M, Kobayashi T, Hirayama T, Hirabayashi T, Yagi T
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋
• [Presentation] CTCF is required for neural development and stochastic expression of clustered Pcdh genes in neurons (2012)
  • Author(s): Hirayama T, Tarusawa E, Yoshimura Y, Galjart N, Yagi T.
  • Organizer: 第３５回日本分子生物学会年会
  • Place of Presentation: 博多
• [Book] Progress in Molecular Biology and Translational Science; The Molecular Biology of Cadherins (2013)
  • Author(s): Hirayama T, Yagi T.
  • Total Pages: 465
  • Publisher: Elsevier Academic Press