Production of neural progenitors in the subventricular zone, and its regulations among species and brain area

• Project/Area Number: 16K07037
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Institute for Developmental Research Aichi Developmental Disability Center
• Principal Investigator: Tabata Hidenori 愛知県医療療育総合センター発達障害研究所, 分子病態研究部, 室長 (80301761)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); 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)
• Keywords: 神経細胞移動 / 神経回路形成 / 神経発生 / 大脳皮質 / 神経幹細胞 / 進化 / 神経科学 / 脳神経疾患

Outline of Final Research Achievements

In the mammalian cerebral cortex, neurons are generated in the ventricular zone and subventricular zone (SVZ). One of the most striking features of fetal human brain is enlargement of SVZ, in which there are special neural progenitors called basal radial glia (bRG) and they are thought to contribute to produce enormous productions of cortical neurons and to acquire the huge brain. In this study, we have identified a gene, JA1, as a potential regulator of bRG production. We clarified (1) JA1 is a positive regulator of bRG production, (2) JA1 is expressed in the bRG itself, (3) and the transcription activity of human regulatory region of JA1 is higher than that of mouse. We identified the responsible region for this difference between human and mouse in intron #1~2. Given the amino acid sequences of JA1 are highly conserved among mammalians, the evolution of regulatory region is thought to be a key to acquire the huge brain in human.

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、ヒトの高度な精神活動の基盤となる巨大脳がいかに進化的に獲得されたかを探索した。先行研究では進化的にヒトで新たに獲得された遺伝子の関与が示唆されたが、本研究ではアミノ酸をコードしない転写調節領域の進化の重要性を解明した点でユニークである。また、本研究で注目したJA1転写調節領域にはヒトの小頭症原因遺伝子の結合配列があり、今後、神経発達障害の病態理解への貢献が期待される。

Research Products

• [Journal Article] Role of Per3, a circadian clock gene, in embryonic development of mouse cerebral cortex.? (2019)
  • Author(s): Noda M, Iwamoto I, Tabata H, Yamagata T, Ito H, Nagata K.
  • Journal Title: Sci. Rep. Volume: 9 Issue: 1 Pages: 5874-5874
  • DOI: 10.1038/s41598-019-42390-9
  • Peer Reviewed / Open Access
• [Journal Article] Spatiotemporally Dependent Vascularization Is Differently Utilized among Neural Progenitor Subtypes during Neocortical Development (2019)
  • Author(s): Komabayashi-Suzuki Mariko、Yamanishi Emiko、Watanabe Chisato、Okamura Megumi、Tabata Hidenori、Iwai Ryota、Ajioka Itsuki、Matsushita Jun、Kidoya Hiroyasu、Takakura Nobuyuki、Okamoto Tadashi、Kinoshita Kazuo、Ichihashi Masamitsu、Nagata Koh-ichi、Ema Masatsugu、Mizutani Ken-ichi
  • Journal Title: Cell Reports Volume: 29 Issue: 5 Pages: 1113-1129
  • DOI: 10.1016/j.celrep.2019.09.048
  • Peer Reviewed / Open Access
• [Journal Article] Biochemical and Morphological Characterization of a Guanine Nucleotide Exchange Factor ARHGEF9 in Mouse Tissues (2018)
  • Author(s): Ibaraki Kyoko、Mizuno Makoto、Aoki Hitomi、Niwa Ayumi、Iwamoto Ikuko、Hara Akira、Tabata Hidenori、Ito Hidenori、Nagata Koh-ichi
  • Journal Title: ACTA HISTOCHEMICA ET CYTOCHEMICA Volume: 51 Issue: 3 Pages: 119-128
  • DOI: 10.1267/ahc.18009
  • NAID: 130007411561
  • ISSN: 0044-5991, 1347-5800
  • Year and Date: 2018-06-26
  • Peer Reviewed
• [Journal Article] Isozyme-Specific Role of SAD-A in Neuronal Migration During Development of Cerebral Cortex (2018)
  • Author(s): Nakanishi Keiko、Niida Hiroyuki、Tabata Hidenori、Ito Tsuyoshi、Hori Yuki、Hattori Madoka、Johmura Yoshikazu、Yamada Chisato、Ueda Takashi、Takeuchi Kosei、Yamada Kenichiro、Nagata Koh-ichi、Wakamatsu Nobuaki、Kishi Masashi、Pan Y Albert、Ugawa Shinya、Shimada Shoichi、Sanes Joshua R、Higashi Yujiro、Nakanishi Makoto
  • Journal Title: Cerebral Cortex Volume: 160 Issue: 9 Pages: 721-721
  • DOI: 10.1093/cercor/bhy253
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Biochemical and Morphological Characterization of a Neurodevelopmental Disorder-Related Mono-ADP-Ribosylhydrolase, MACRO Domain Containing 2 (2018)
  • Author(s): Ito Hidenori、Morishita Rika、Mizuno Makoto、Kawamura Noriko、Tabata Hidenori、Nagata Koh-ichi
  • Journal Title: Developmental Neuroscience Volume: 40 Issue: 3 Pages: 278-287
  • DOI: 10.1159/000492271
  • Peer Reviewed
• [Journal Article] A Prdm8 target gene Ebf3 regulates multipolar-to-bipolar transition in migrating neocortical cells (2018)
  • Author(s): Iwai Ryota、Tabata Hidenori、Inoue Mayuko、Nomura Kei-ichiro、Okamoto Tadashi、Ichihashi Masamitsu、Nagata Koh-ichi、Mizutani Ken-ichi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 495 Issue: 1 Pages: 388-394
  • DOI: 10.1016/j.bbrc.2017.11.021
  • Peer Reviewed / Open Access
• [Journal Article] Possible involvement of a cell adhesion molecule, Migfilin, in brain development and pathogenesis of autism spectrum disorders (2017)
  • Author(s): Ishizuka Kanako、Tabata Hidenori、Ito Hidenori、Kushima Itaru、Noda Mariko、Yoshimi Akira、Usami Masahide、Watanabe Kyota、Morikawa Mako、Uno Yota、Okada Takashi、Mori Daisuke、Aleksic Branko、Ozaki Norio、Nagata Koh-ichi
  • Journal Title: Journal of Neuroscience Research Volume: 96 Issue: 5 Pages: 789-802
  • DOI: 10.1002/jnr.24194
  • Peer Reviewed / Open Access
• [Journal Article] MUNC18-1 gene abnormalities are involved in neurodevelopmental disorders through defective cortical architecture during brain development (2017)
  • Author(s): Hamada Nanako、Iwamoto Ikuko、Tabata Hidenori、Nagata Koh-ichi
  • Journal Title: Acta Neuropathologica Communications Volume: 5 Issue: 1 Pages: 92-92
  • DOI: 10.1186/s40478-017-0498-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dnmt1-dependent Chk1 pathway suppression is protective against neuron division (2017)
  • Author(s): Oshikawa Mio、Okada Kei、Tabata Hidenori、Nagata Koh-ichi、Ajioka Itsuki
  • Journal Title: Development Volume: 144 Issue: 18 Pages: 3303-3314
  • DOI: 10.1242/dev.154013
  • Peer Reviewed
• [Journal Article] Extracellular Signals induce Glycoprotein M6a Clustering of Lipid-rafts and associated Signaling Molecules. (2017)
  • Author(s): Honda A, Ito Y, Takahashi-Niki, Matsushita N, Nozumi M, Tabata H, Takeuchi K, Igarashi M
  • Journal Title: J Neurosci. Volume: 37(15) Issue: 15 Pages: 4046-4064
  • DOI: 10.1523/jneurosci.3319-16.2017
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of a circadian-relevant gene NR1D1 in brain development: possible involvement in the pathophysiology of autism spectrum disorders. (2017)
  • Author(s): Goto, M., Mizuno, M., Matsumoto, A., Yang, Z., Jimbo, E.F., Tabata, H., Yamagata, T., Nagata, K.-I.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 43945-43945
  • DOI: 10.1038/srep43945
  • Peer Reviewed / Open Access
• [Journal Article] Prdm16 is crucial for progression of the multipolar phase during neural differentiation of the developing neocortex. (2017)
  • Author(s): Inoue M, Iwai R, Tabata H, Konno D, Komabayashi-Suzuki M, Watanabe C, Iwanari H, Mochizuki Y, Hamakubo T, Matsuzaki F, Nagata K-I, Mizutani K-I
  • Journal Title: Development Volume: 144 Issue: 3 Pages: 385-399
  • DOI: 10.1242/dev.136382
  • Peer Reviewed
• [Journal Article] Role of a heterotrimeric G-protein, Gi2, in the corticogenesis: possible involvement in periventricular nodular heterotopia and intellectual disability. (2016)
  • Author(s): Hamada, N., Negishi, Y., Mizuno, M., Miya, F., Hattori, A., Okamoto, N., Kato, M., Tsunoda, T., Yamasaki, M., Kanemura, Y., Kosaki, K., Tabata, H., Saitoh, S., Nagata, K.-I.
  • Journal Title: J. Neurochem. Volume: 140 Issue: 1 Pages: 82-95
  • DOI: 10.1111/jnc.13878
  • Peer Reviewed
• [Journal Article] Essential role of the nuclear isoform of RBFOX1, a candidate gene for autism spectrum disorders, in the brain development. (2016)
  • Author(s): Hamada N, Ito H, Nishijo T, Iwamoto I, Morishita R, Tabata H, Momiyama T, Nagata K-I
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 30805-30805
  • DOI: 10.1038/srep30805
  • Peer Reviewed / Open Access
• [Presentation] Possible role of the evolutional changes in the transcriptional activity to acquire the huge brain in humans (2019)
  • Author(s): Hidenori Tabata, Tsuyoshi Hachiya, Kouji Shimoda, Kanehiro Hayashi Koh-ichi Nagata, Yasubumi Sakakibara, Kazunori Nakajima
  • Organizer: Neuro2019
• [Presentation] 大脳皮質神経細胞の産生調節機構と、その進化 ～マウスとヒトのゲノム配列を用いた機能解析 (2018)
  • Author(s): 田畑秀典、八谷 剛史、林 周宏、永田 浩一、榊原 康文、仲嶋 一範
  • Organizer: 第41回日本分子生物学会年会
  • Invited
• [Presentation] Migration of astrocyte progenitors and its relationship with blood vessels in the developing cerebral cortex. (2018)
  • Author(s): 田畑秀典
  • Organizer: 第10回NAGOYAグローバルリトリート
  • Invited
• [Presentation] アストロサイト前駆細胞の移動過程における血管の役割 (2018)
  • Author(s): 田畑秀典
  • Organizer: 第２回Neuro-Vascular研究会
• [Presentation] 哺乳類大脳皮質発生過程におけるアストロサイト前駆細胞の移動と血管化 (2017)
  • Author(s): 田畑秀典
  • Organizer: 生命科学系学会合同年次大会（ConBio2017）ワークショップ
  • Invited
• [Presentation] 子宮内電気穿孔法とライブイメージングを用いた大脳皮質発生機構の解析 (2017)
  • Author(s): 田畑秀典
  • Organizer: 第39回神経組織培養研究会
  • Invited
• [Presentation] 大脳皮質発生過程における2次的神経細胞産生部位としての脳室下帯の成り立ちと脳進化 との関連 (2016)
  • Author(s): 田畑秀典
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-12-01
  • Invited
• [Presentation] Erratic migration: a unique migratory behavior of astrocyte progenitors. (2016)
  • Author(s): Tabata H, Sasaki M, Inaguma Y, Ito H, Takebayashi H, Ema M, Ikenaka K, Nagata K, Nakajima K
  • Organizer: Neuroscience 2016
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-11-14
  • Int'l Joint Research