Postnatal brain development regulated by intellectual disability-associated protein complex

• Project/Area Number: 24650199
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kyushu University
• Principal Investigator: SAKAI YASUNARI 九州大学, 大学病院, 講師 (10380396)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 精神遅滞 / DEAF1 / 複合体 / FMRP / 分子シグナル / 脳 / 発達遅滞 / 神経軸索 / FMR1 / 神経成熟 / 細胞内局在 / タンパク質相互作用 / 発達 / タンパク質複合体

Outline of Final Research Achievements

We analyzed the expression patterns of intellectual disability-associated protein DEAF1 in the postnatal period of wild-type mouse brain. Immunofluorescence study revealed that DEAF1 was highly expressed in the neuronal dendrites of cerebral cortex and hippocampus. Commercially available antibodies were not able to enrich DEAF1 in the immunoprecipitation assays using the mouse brain extracts. Thus DEAF1-FMRP complex was not detected in this study. Knockdown and overexpression of DEAF1 in Neuro2a cells suggested that DEAF1 is involved in the process for extension of dendrites. We are currently investigating the molecular mechanisms underlying these neuronal phenotypes.

Research Products

• [Journal Article] Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary movements with severe developmental delay (2015)
  • Author(s): Saitsu H, Fukai R, Ben-Zeev B, Sakai Y, Mimaki M, Okamoto N, Suzuki Y, Monden Y, Saito H, Tziperman B, Torio M, Akamine S, Takahashi N, Osaka H, Yamagata T, Nakamura K, Tsurusaki Y, Nakashima M, Miyake N, Shiina1 M, Ogata K, Matsumoto N.
  • Journal Title: Eur J Hum Genet Volume: 23
  • Peer Reviewed
• [Journal Article] Periodic epileptiform discharges in children with advanced stages of progressive myoclonic epilepsy (2015)
  • Author(s): Isobe N, Sakai Y, Kira R, Sanefuji M, Ishizaki Y, Sakata A, Sasazuki M, Torio M, Akamine S, Torisu H, Hara T
  • Journal Title: Clin EEG Neurosci Volume: 46
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Kawasaki disease-specific molecules in the sera are linked to microbe-associated molecular patterns in the biofilms (2014)
  • Author(s): Kusuda T, Nakashima Y, Murata K, Kanno S, Nishio H, Saito M, Tanaka T, Yamamura K, Sakai Y, Takada H, Miyamoto T, Mizuno Y, Ouchi K, Waki K, Hara T
  • Journal Title: PLoS One Volume: 9
  • Peer Reviewed
• [Journal Article] Testicular sex cord-stromal tumor in a boy with 2q37 deletion syndrome (2014)
  • Author(s): Sakai Y, Souzaki R, Yamamoto H, Matsushita Y, Nagata H, Ishizaki Y, Torisu H, Oda Y, Taguchi T, Shaw CA, Hara T
  • Journal Title: BMC Med Genomics Volume: 7 Pages: 19-19
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Testicular sex cord-stromal tumor in a boy with 2q37 deletion syndrome (2014)
  • Author(s): Sakai Y, Souzaki R, Yamamoto H, Matsushita Y, Nagata H, Oda Y, Taguchi T, Shaw CA, Hara T
  • Journal Title: BMC Med Genomics Volume: 7
  • Peer Reviewed
• [Journal Article] Neuroendocrine phenotypes in a boy with 5q14 deletion syndrome implicate the regulatory roles of myocyte-specific enhancer factor 2C in the postnatal hypothalamus. (2013)
  • Author(s): Sakai, Y., Ohkubo, K., Matsushita, Y., Akamine, S., Ishizaki, Y., Torisu, H., Ihara, K., Sanefuji, M., Kim, M.S., Lee, K.U., Shaw, C.A., Lim, J., Nakabeppu, Y., and Hara, T.
  • Journal Title: Eur J Med Genet Volume: 59 Issue: 9 Pages: 475-783
  • DOI: 10.1016/j.ejmg.2013.06.009
  • Peer Reviewed
• [Journal Article] Systemic vascular phenotypes of Loeys-Dietz syndrome in a child carrying a de novo R381P mutation in TGFBR2: a case report. (2013)
  • Author(s): Uike K, Matsushita Y, Sakai Y, Togao O, Nagao M, Ishizaki Y, Nagata H, Yamamura K, Torisu H, Hara T.
  • Journal Title: BMC Research Notes Volume: 6 Issue: 1 Pages: 456-456
  • DOI: 10.1186/1756-0500-6-456
  • Peer Reviewed
• [Presentation] Hypothalamic dysfunction in 5q14 deletion syndrome (2013)
  • Author(s): Sakai Y, Ohkubo K, Matsushita Y, Hara T
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, USA
• [Presentation] 自閉症発症に関与する分子シグナルの探索 (2013)
  • Author(s): 酒井康成
  • Organizer: 第55回日本小児神経学会学術集会
  • Place of Presentation: 大分
  • Invited
• [Presentation] The network approach towards identifying the molecular pathogenesis of autism and related disorders
  • Author(s): 酒井康成
  • Organizer: 第35回日本分子生物学会年会（精神のオミックス・ワークショップ）
  • Place of Presentation: 福岡
  • Invited
• [Presentation] Proteomic approaches deciphering the molecular pathways for autism spectrum disorders
  • Author(s): Yasunari Sakai, Chad A Shaw, Zaina Al-Mohtaseb, Diana V Dugas, Toshiro Hara:
  • Organizer: 第54回日本小児神経学会総会（English Session）
  • Place of Presentation: 札幌
• [Presentation] MEF2C遺伝子を含む染色体5q14.3領域の欠失を認めた重度精神遅滞の14歳男児例
  • Author(s): 酒井康成，鳥巣浩幸，實藤雅文，山口結，石崎義人，鳥尾倫子，磯部菜摘，原寿郎
  • Organizer: 第54回日本小児神経学会総会
  • Place of Presentation: 札幌