Elucidation of the intracellular epigenetic modification and extracellular microenvironment regulating the development of the central nervous system

2014 Fiscal Year Final Research Report

• Project/Area Number: 24300119
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TAGA Tetsuya 東京医科歯科大学, 難治疾患研究所, 教授 (40192629)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 神経幹細胞 / 発生・分化 / エピゲノム / 自己複製 / ニッチ / 神経科学 / 疾患モデルマウス / シグナル伝達

Outline of Final Research Achievements

Gasc1 gene encodes a histone H3 lysine 9 (H3K9) demethylating enzyme, which we previously found is expressed in post-mitotic neurons in the mouse brain. We showed that GASC1 hypomorphic mutant mice exhibit mental disorder-like abnormal behaviors. In the present study, we have newly detected increased dendritic spine densities of the mutant hippocampal neurons. Electrophysiological studies on hippocampal slices have further demonstrated increased long-term potentiation. Further studies will enable us to discuss the cause of human neurological/psychiatric symptoms and future drug discoveries. We have also found that one of the ten-eleven translocation (TET) proteins, TET3, is involved in the timing of astrocyte development most likely through oxidization of the 5-methylcytosine.
We have also provided a novel molecular mechanism for NSC self-renewal in which one of the growth promoting signaling components, cyclin D1, which is induced by FGF2- and Wnts inhibits astrocyte differentiation.

Free Research Field

幹細胞生物学