EPIGENETIC REGULATION OF CELL CYCLE KINETICS OF MURINE NEURONAL STEM CELLS BY HISTONE DEACETYLASE

• Project/Area Number: 20390299
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Keio University
• Principal Investigator: TAKAHASHI Takao Keio University, 医学部, 教授 (80171495)
• Co-Investigator(Kenkyū-buntansha): KOSAKI Kenjiro 慶應義塾大学, 医学部, 准教授 (30234743) ; MITSUHASHI Takayuki 慶應義塾大学, 医学部, 講師 (80338110)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2010: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2009: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2008: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: エピジェネティクス / 大脳皮質発生 / 神経前駆細胞 / マウス / 細胞周期 / ヒストン脱アセチル化 / 神経発生 / 大脳皮質

Research Abstract

Epigenetic mechanisms is considered to be a putative machinery for controlling cell cycle kinetics of neuronal progenitor cells (NPCs). We investigated effects of overfunction of histone deacetylase in cell cycle regulation in NPCs which forms cerebral neocortex in vivo. Double-transgenic mice were generated that were capable of overexpressing histone deacetylase Sir2 proteins in NPCs in time dependent manner. We detected transient shortening of the length of the cell cycle on embryonic day (E) 16 as Sir2 were overexpressed in NPCs by doxycycline administration starting from E14 to E16. This result indicate that deacetylation of histone may play a critical role in production of projection neurons in neocortex as well as pathogenesis of cerebral cortical abnormality.

Research Products

• [Journal Article] In utero exposure to dioxin causes neocortical dysgenesis through the actions of p27^<Kip1> (2010)
  • Author(s): Mitsuhashi T, Yonemoto J, Sone H, Kosuge Y, Kosaki K, Takahashi T
  • Journal Title: Proc Natl Acad Sci USA 107(37) Pages: 16331-5
  • Peer Reviewed
• [Journal Article] In utero exposure to dioxin causes neocortical dysgenesis through the actions of p27Kip1. (2010)
  • Author(s): Mitsuhashi T, Yonemoto J, Sone H, Kosuge Y, Kosaki K, Takahashi T.
  • Journal Title: Proc Natl Acad Sci USA Volume: 107 Pages: 16331-16335
  • Peer Reviewed
• [Journal Article] Genetic Regulation of Proliferation/Differentiation Characteristics of Neural Progenitor Cells in the Developing Neocortex. (2009)
  • Author(s): Mitsuhashi T, Takahashi T
  • Journal Title: Brain & Development 31(7) Pages: 553-7
  • NAID: 10025580725
• [Journal Article] Caudal regression and tracheoesophageal malformation induced by adriamycin : A novel chick model of VATER association. (2009)
  • Author(s): Naito Y, Kimura T, Aramaki M, Izumi K, Okada Y, Suzuki H, Takahashi T, Kosaki K
  • Journal Title: Pediatr Res 65 Pages: 607-12
  • Peer Reviewed
• [Journal Article] Effects of the CYP2D6*10 alleles and co-medication with CYP2D6-dependent drugs on risperidone metabolism in patients with schizophrenia. (2009)
  • Author(s): Yagihashi T, Mizuno M, Chino B, Sato Y, Sakuma K, Takebayashi T, Takahashi T, Kosaki K
  • Journal Title: Hum Psychopharmacol. 24 Pages: 301-8
  • Peer Reviewed
• [Journal Article] Two distinctive classic genetic syndromes, 22q11.2 deletion syndrome and Angelman syndrome, occurring within the same family. (2009)
  • Author(s): Kosaki R, Migita O, Takahashi T, Kosaki K
  • Journal Title: Am J Med Genet 149A Pages: 702-5
  • Peer Reviewed
• [Journal Article] Genetic Regulation of Proliferation/Differentiation Characteristics of Neural Progenitor Cells in the Developing Neocortex. (2009)
  • Author(s): Mitsuhashi T, Takahashi T.
  • Journal Title: Brain & Development 31(7) Pages: 553-557
  • NAID: 10025580725
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): Mitsuhashi T, Takahashi T.
  • Journal Title: Cell cycle. In Encyclopedia of Neuroscience.(Springer-Verlag, Berlin) Pages: 588-591
• [Journal Article] Genetic Regulation of Proliferation/Differentiation Characteristics of Neural Progenitor Cells in the Developing Neocortex. (2009)
  • Author(s): Mitsuhashi T, Takahashi T.
  • Journal Title: Brain & Development (In press)
  • NAID: 10025580725
  • Peer Reviewed
• [Journal Article] Split hand foot malformation with whorl-like pigmentary pattern : Phenotypic expression of somatic mosaicism for the p63 mutation. (2008)
  • Author(s): Kosaki R, Naito Y, Torii C, Takahashi T, Nakajima T, Kosaki K
  • Journal Title: Am J Med Genet 146 Pages: 2574-2577
  • Peer Reviewed
• [Presentation] 発達障害の克服を目指す脳研究の抱える問題点、困難さについて (2011)
  • Author(s): 高橋孝雄
  • Organizer: 精神・神経疾患の克服を目指す脳科学研究(健康脳)ワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2011-02-08
• [Presentation] ダイオキシン胎内曝露によるp27Kip1を介した大脳皮質構築異常:数学モデルを用いた解析 (2010)
  • Author(s): 三橋隆行
  • Organizer: 第41回慶應ニューロサイエンス研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-06
• [Presentation] Genetic/Environment Interactions for Human Brain Development (2010)
  • Author(s): Takahashi T.
  • Organizer: The 11th International Child Neurology Congress
  • Place of Presentation: Cairo, Egypt
  • Year and Date: 2010-05-07
• [Presentation] Genetics/Environment interactions for human development. (2010)
  • Author(s): Takahashi T
  • Organizer: XIth World Congress of International Child Neurology Association
  • Place of Presentation: Cairo, Egypt
  • Year and Date: 2010-05-05
• [Presentation] Developmental regulation of acetylation statuses of histone proteins in neural progenitor cells of murine cerebral wall. (2010)
  • Author(s): Mitsuhashi T, Takahashi T
  • Organizer: The 6th Congress of Asian Society for Pediatric Research
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2010-04-17
• [Book] 発達科学入門 第2巻 I部(1.胎児の発達) (2011)
  • Author(s): 三橋隆行、高橋孝雄
  • Publisher: 東京大学出版会(印刷中)
• [Book] 発達科学入門 第2巻 I部 1.胎児の発達 (2011)
  • Author(s): 三橋隆行、高橋孝雄
  • Publisher: 東京大学出版会(印刷中)
• [Book] Encyclopedia of Neuroscience. Volume III(Binder MD, Hirokawa N, Windhorst U, Hirsch MC (eds), Murakami F (section ed).) (Cell cycle) (2009)
  • Author(s): Mitsuhashi T, Takahashi T
  • Publisher: Springer-Verlag, Berlin
• [Book] Cell cycle. In Encyclopedic Reference of Neuroscience. (2009)
  • Author(s): Mitsuhashi T, Takahashi T.
  • Publisher: Springer-Verlag, Berlin(In press)
• [Book] Progress in Epileptic Disorders Series(Biology of Seizure Susceptibility in Developing Brain. Vol.6) (2008)
  • Author(s): Takahashi T, Fukuyama Y (eds).
  • Total Pages: 232
  • Publisher: John Libbey Eurotext, Montrouge (Paris)
• [Remarks] ホームページ等
  • URL: http://www.med.keio.ac.jp/rdb/med/view.php?i=32
• [Remarks]
  • URL: http://www.med.keio.ac.jp/rdb/med/view.php?i=32