Developmental epigenetic regulation for neuronal diversity

• Project/Area Number: 26640012
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience
• Research Institution: University of Yamanashi (2015-2016); Osaka University (2014)
• Principal Investigator: TOYODA Shunsuke 山梨大学, 総合研究部, 医学研究員 (10727415)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 神経細胞 / エピジェネティクス / 多様性 / 神経回路 / iPS細胞

Outline of Final Research Achievements

By conducting DNA methylation analysis from the embryo to the postnatal brain, establishment of the iPS cell line from the embryonic lethal mouse and generation of the chimeric mouse, and gene expression analysis and morphological analysis at the single neuron level, we revealed that differential DNA methylation dependent on DNA methylation enzyme Dnmt3b regulates the stochastic expression of the clustered protocadherin genes in Purkinje cells and that it is involved in pattern formation of dendrites. In addition, as a collaborative research, we found that the epigenetic regulation at the developmental stage is also involved in the formation of reciprocal synaptic connections dependent on the cell lineage of the cerebral cortex by performing double whole cell recording in the brain of chimeric mice.

Research Products

• [Journal Article] Establishment of high reciprocal connectivity between clonal cortical neurons is regulated by the Dnmt3b DNA methyltransferase and clustered protocadherins. (2016)
  • Author(s): Tarusawa E., Sanbo M., Okayama A., Miyashita T., Kitsukawa T., Hirayama T., Hirabayashi T., Hasegawa S., Kaneko R., Toyoda S., Kobayashi T., Kato-Itoh M., Nakauchi H., Hirabayashi M., Yagi T., Yoshimura Y.
  • Journal Title: BMC Biology Volume: 14 Issue: 1 Pages: 103-103
  • DOI: 10.1186/s12915-016-0326-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] 神経細胞の多様化に重要な発生初期のエピジェネティック制御 クラスター型プロトカドヘリン遺伝子の確率的発現 (2014)
  • Author(s): 豊田峻輔, 八木健
  • Journal Title: 実験医学 Volume: 32 (14) Pages: 2263-2266
• [Presentation] 神経細胞の多様化に重要な発生期のエピジェネティック制御 (2015)
  • Author(s): 豊田峻輔
  • Organizer: BMB2015（第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会）
  • Place of Presentation: 神戸ポートアイランド（兵庫県・神戸市）
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] Developmental epigenetic modification regulates stochastic expression of clustered Protocadherin genes, generating single neuron diversity (2014)
  • Author(s): Toyoda S, Yagi T.
  • Organizer: 9th FENS Forum of Neuroscience
  • Place of Presentation: イタリア ミラノ
  • Year and Date: 2014-07-05 – 2014-07-09
• [Remarks] 豊田峻輔 ホームページ
  • URL: http://researchmap.jp/toyoda02/
• [Remarks] 山梨大学医学部・大学院総合研究部 生理学講座神経生理学教室 ホームページ
  • URL: http://www.med.yamanashi.ac.jp/basic/physio02/Kitamura_Lab_j/Top_j.html
• [Remarks] 山梨大学医学部・大学院総合研究部 生理学講座第２教室 ホームページ
  • URL: http://www.med.yamanashi.ac.jp/basic/physio02/Kitamura_Lab_j/Top_j.html