Identification and characterization of a new regulator of astrocyte differentiation

• Project/Area Number: 15K06792
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: National Rehabilitation Center for Persons with Disabilities
• Principal Investigator: Nagao Motoshi 国立障害者リハビリテーションセンター(研究所), 研究所 運動機能系障害研究部, 研究室長 (00359671)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 神経幹細胞 / グリア / アストロサイト / 転写因子 / 大脳新皮質

Outline of Final Research Achievements

Multipotent neural precursor cells (NPCs) generate astrocytes at late stages of mammalian neocortical development, but the underlying mechanisms remain poorly understood. Here I show that Zbtb20 regulates astrocyte specification in the mouse neocortex. Zbtb20 is highly expressed in late-stage NPCs and their astrocytic progeny. Overexpression and knockdown of Zbtb20 promote and suppress astrocytogenesis, respectively. Astrocyte induction by Zbtb20 is suppressed by knockdown of Sox9 or NFIA. Furthermore, in the astrocyte lineage, Zbtb20 directly represses the expression of Brn2, which encodes a protein necessary for upper-layer neuron specification. Zbtb20 is thus a key determinant of astrocytogenesis, in which it collaborates with Sox9 and NFIA and acts in part through direct repression of Brn2 expression.

Research Products

• [Journal Article] Chd7 collaborates with Sox2 to regulate activation of oligodendrocyte precursor cells after spinal cord injury (2017)
  • Author(s): Doi T, Ogata T, Yamauchi J, Sawada Y, Tanaka S, Nagao M
  • Journal Title: J Neurosci Volume: 37(43) Issue: 43 Pages: 10290-10309
  • DOI: 10.1523/jneurosci.1109-17.2017
  • Peer Reviewed
• [Journal Article] The crucial role of Erk2 in demyelinating inflammation in the central nervous system. (2016)
  • Author(s): Okazaki R, Doi T, Hayakawa K, Morioka K, Imamura O, Takishima K, Hamanoue M, Sawada Y, Nagao M, Tanaka S, Ogata T
  • Journal Title: J Neuroinflammation Volume: 13 Issue: 1 Pages: 235-239
  • DOI: 10.1186/s12974-016-0690-8
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Zbtb20 promotes astrocytogenesis during neocortical development (2016)
  • Author(s): Nagao, M., Ogata, T., Sawada, Y., Gotoh, Y.
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 11102-11102
  • DOI: 10.1038/ncomms11102
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Chd7 collaborates with Sox2 to regulate activation of oligodendrocyte precursor cells after spinal cord injury. (2017)
  • Author(s): Doi T, Ogata T, Sawada Y, Tanaka S, Nagao M.
  • Organizer: Neuroscience2017
  • Int'l Joint Research
• [Presentation] Regulation of astrocyte production in the developing mouse neocortex. (2017)
  • Author(s): Lanjakornsiripan D, Furutachi S, Pior B-J, Kishi Y, Hirabayashi Y, Nagao M, Gotoh Y.
  • Organizer: XIII European Meeting on Glial Cells in Health and Disease
  • Int'l Joint Research / Invited
• [Presentation] アストロサイト分化を制御する新しい転写因子 (2015)
  • Author(s): 長尾元史
  • Organizer: 第３８回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-28
  • Invited
• [Remarks] 国立障害者リハビリテーションセンター
  • URL: http://www.rehab.go.jp