Development of the blood vessel regeneration system utilizing Zic family proteins

• Project/Area Number: 15K15019
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Nagasaki University
• Principal Investigator: ARUGA Jun 長崎大学, 医歯薬学総合研究科(医学系), 教授 (10232076)
• Co-Investigator(Renkei-kenkyūsha): NAKAGAWA Shinsuke 長崎大学, 医歯薬学総合研究科(医学系), 講師 (10404211) ; TATSUMI Rie 長崎大学, 医歯薬学総合研究科(医学系), 助教 (40584727) ; HATAYAMA Minoru 長崎大学, 医歯薬学総合研究科(医学系), 助教 (50443007)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 神経血管ユニット / 遺伝子発現制御 / 転写因子 / 虚血性脳疾患 / 動脈硬化 / 遺伝子ターゲッティング / 間葉性幹細胞 / 疾患モデル動物 / 脳血管系 / 発生 / 高脂血症 / 血液脳関門

Outline of Final Research Achievements

We and others recently reported that Zic family zinc finger transcription factors are expressed in brain vessel-constituting cells and regulate the gene expression of ApoE, an atherosclerosis protective protein. We therefore planned to clarify the role of Zic genes in neurovascular units and the expression change of the Zic family proteins among normal, atherosclerotic, and ischemic brain vessels. The results indicated that the Zic family proteins produced in the vascular pericytes, vascular endothelial cells and blood vessel progenitor cells in a cell-type specific manner. We also found that some Zic proteins have critical role of in the development of brain vessels. These findings paved a way to develop a regulatory system utilizing the biological activities of Zic family proteins.

Research Products

• [Journal Article] Autism-like behaviors and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice. (2017)
  • Author(s): Morimura, N., Yasuda, H., Yamaguchi K., Katayama, K., Hatayama, M., Tomioka, N.H., Odagawa, M., Kamiya, A., Iwayama, Y., Maekawa, M., Nakamura, K., Matsuzaki, H., Tsujii, M., Yamada, K., Yoshikawa, T., Aruga, J.
  • Journal Title: Nature Communications Volume: 印刷中
  • NAID: 130007901310
  • Peer Reviewed / Open Access
• [Presentation] Zic遺伝子ファミリーによる脳血管系の発生制御 (2017)
  • Author(s): 渡邉新太、畑山 実、中川慎介、巽理恵、有賀 純
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎ブリックホール（長崎県長崎市）
  • Year and Date: 2017-03-15
• [Presentation] Roles of Zic family zinc finger proteins in development and maintenance of the blood-brain-barrier (2015)
  • Author(s): J. ARUGA, M. HATAYAMA, S. NAKAGAWA, R. TATSUM
  • Organizer: Society for Neuroscience Annual Meeting
  • Place of Presentation: シカゴ（米国）
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Remarks] 「Zic」脳科学辞典 （有賀純、畑山実、日本神経科学学会編）
  • URL: https://bsd.neuroinf.jp/wiki/Zic