Mechanism of neural circuit plasticity investigated from cell-type specific chromatin dynamics of juvenile brain

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K14781
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Genetics/Chromosome dynamics
• Research Institution: Niigata University
• Principal Investigator: SAKAI Akiko 新潟大学, 医歯学総合研究科, 日本学術振興会特別研究員 (70532745)
• Research Collaborator: NAKATO Ryuichiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 臨界期 / 抑制性ニューロン / PV細胞 / ChIP-seq / 細胞種特異的トランスクリプトーム / クロマチン / 転写制御 / Otx2

Outline of Final Research Achievements

This study aimed to clarify gene expression and chromatin dynamics specific to interneurons (PV cells) that govern development of brain function depending on juvenile experience in mammals. Downstream target genes of Otx2 homeoprotein necessary for development of PV cells were identified comprehensively using ChIP-seq and interneuron-specific RNA-seq. Important functions of Otx2 were suggested to be promoting functional development for fast-spiking property characteristic to PV cells as well as homeostatic regulation. Moreover, functional analysis of a cohesin-related factor indicated importance of regulating chromatin structure in maturation of PV cells.

Free Research Field

クロマチン生物学

Academic Significance and Societal Importance of the Research Achievements

脳の成長には、神経回路の興奮性を調節する抑制性の神経細胞の働きが不可欠である。本研究では、経験に応じて脳の発達を促すOtx2が調節し得る遺伝子として、抑制性神経細胞の機能に必要な遺伝子群や、細胞の恒常性を保つ抗酸化遺伝子を新たに発見した。また、遺伝子調節の背景にある染色体の構造の調節の重要性も見出した。本研究の成果は、脳の成長のしくみと、その異常による精神疾患の原因の解明につながると期待される。