Functional analysis of DNA methyltransferases in post-mitotic neuron

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430083
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Namihira Masakazu 国立研究開発法人産業技術総合研究所, バイオメディカル研究部門, 研究グループ長 (60379534)
• Co-Investigator(Renkei-kenkyūsha): EBIHARA Tatsuhiko 産業技術総合研究所, バイオメディカル研究部門, 主任研究員 (00344119)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 神経科学 / エピジェネティクス / DNAメチル化 / 神経細胞 / 神経幹細胞 / 精神疾患

Outline of Final Research Achievements

To investigate the function of DNA methyltransferases in neural cells, we deleted dnmt1 gene in these cells and examined the phenotype in vitro and in vivo. We found that prenatal deletion of DNA methyltransferase 1 (Dnmt1) in neural stem cells causes the impairment of neurogenesis in the adult mouse brain. Moreover, these mice exhibited anxiety-like behavior. In addition, in DNMT1 deficient neurons, axonal elongation tends to be accelerated compared to that in wild type neurons, suggesting that DNMT1 regulates neurite outgrowth during neuronal maturation. Furthermore, conditional knockout mice that dnmt1 is deleted in post-mitotic neuron exhibited hyperactivity at adult stage. Thus, these results imply that DNA methyltranseferases in neural cells play an important role in neuronal development and its mutation links to psychiatric diseases.

Free Research Field

神経科学