Study of non-apoptotic programmed cell death during embryogenesis in mice

• Project/Area Number: 15K14519
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses
• Principal Investigator: TSUJIMOTO YOSHIHIDE 地方独立行政法人大阪府立病院機構大阪府立成人病センター(研究所), その他部局等, 研究所長 (70132735)
• Research Collaborator: IMAGAWA Yusuke 大阪府立成人病センター研究所, 研究員 (20614770) ; MATSUOKA Yosuke 大阪府立成人病センター研究所, 非常勤研究員 (60263258)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: プログラム細胞死 / ネクローシス / アポトーシス / オートファジー / 生体イメージング / 形態形成 / 個体発生 / 骨形成 / 心臓 / イメージング

Outline of Final Research Achievements

Programmed cell death has a crucial role in various biological events, including developmental morphogenesis. Recent evidence indicates that necrosis contributes to programmed cell death in addition to apoptosis. For imaging physiological necrosis in vivo, we developed the vital staining method using propidium iodide to identify cells with plasma membrane disruption (necrotic cells) in mouse embryos. We discover that non-apoptotic programmed death occur in various tissues and in various stages during embryogenesis. We focused on a form of necrosis at the bone surface and found the death does not occur in embryos with deficiency of the autophagy-related gene Atg9a, although it is unaffected by Atg5 knockout. We also find abnormalities of the bone surface in Atg9a knockout mice, suggesting an important role of Atg9a-dependent necrosis in bone surface formation. These findings suggest that necrosis has an active role in developmental morphogenesis.

Research Products

• [Journal Article] MPP+ induces necrostatin-1- and ferrostatin-1-sensitive necrotic death of neuronal SH-SY5Y cells. (2017)
  • Author(s): Ito K, Eguchi Y, Imagawa Y, Akai S, Mochizuki H, Tsujimoto Y.
  • Journal Title: Cell Death Discovery Volume: 3 Issue: 1 Pages: 17013-17013
  • DOI: 10.1038/cddiscovery.2017.13
  • Peer Reviewed / Open Access
• [Journal Article] High expression of α-synuclein in damaged mitochondria with PLA2G6 dysfunction. (2016)
  • Author(s): Sumi-Akamaru, H., Beck, G., Shinzawa, K., Kato, S., Riku, Y., Yoshida, M., Fujimura, H., Tsujimoto, Y., Sakoda, S. and Mochizuki, H.
  • Journal Title: Acta Neuropathol. Comm. Volume: 4 Issue: 1 Pages: 27-27
  • DOI: 10.1186/s40478-016-0298-3
  • Peer Reviewed / Open Access
• [Journal Article] Progressive axonal degeneration of striatonigral dopaminergic neurons in calcium-independent phospholipase A2beta knockout mice (2016)
  • Author(s): Beck, G., Shinzawa, K., Hayakawa, H., Baba, K., Sumi-Akamaru, H., Tsujimoto, Y. and Mochizuki, H.
  • Journal Title: PLOS One Volume: 11 Issue: 4 Pages: e0153789-e0153789
  • DOI: 10.1371/journal.pone.0153789
  • Peer Reviewed / Open Access
• [Journal Article] Golgi membrane-associated degradation pathway in yeast and mammals (2016)
  • Author(s): H. Yamaguchi, S. Arakawa, T. Kanaseki, T. Miyatsuka, Y. Fujitani, H. Watada, Y. Tsujimoto, S. Shimizu
  • Journal Title: EMBO J. Volume: 35 Issue: 18 Pages: 1991-2007
  • DOI: 10.15252/embj.201593191
  • Peer Reviewed
• [Journal Article] Vital staining for cell death identifies Atg9a-dependent necrosis in developmental bone formation in mouse (2016)
  • Author(s): Imagawa Y, Saitoh T, Tsujimoto Y
  • Journal Title: Nat Commun Volume: 7 Issue: 1 Pages: 13391
  • DOI: 10.1038/ncomms13391
  • NAID: 120006535064
  • URL: https://tokushima-u.repo.nii.ac.jp/records/2005597
  • Peer Reviewed / Open Access
• [Journal Article] Deficiency of calcium-independent phospholipase A2 beta induces brain iron accumulation through upregulation of divalent metal transporter 1 (2015)
  • Author(s): Beck, G., Shinzawa, K., Hayakawa, H., Baba, K., Yasuda, T., Sumi-Akamaru, H., Tsujimoto, Y. and Mochizuki, H.
  • Journal Title: PLOS One Volume: 10 Issue: 10 Pages: 1-14
  • DOI: 10.1371/journal.pone.0141629
  • Peer Reviewed / Open Access
• [Presentation] MPP+により誘導される新たなネクローシス型神経細胞死 (2016)
  • Author(s): 伊藤奎亮, 恵口豊, 今川佑介, 赤井周司, 辻本賀英
  • Organizer: 第３９回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] HDAC阻害剤による非アポトーシス型細胞死の抑制 (2015)
  • Author(s): 新沢 康英, 辻本 賀英
  • Organizer: に本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] Cyclophilin D欠損マウスを用いた尿路結石形成におけるミトコンドリア傷害機序の解明 (2015)
  • Author(s): 伊藤 靖彦,安井 孝周, 新美 和寛, 海野 怜, 田口 和己, 安藤 亮介, 岡田 淳志, 戸澤 啓一, 辻本 賀英, 郡 健二郎
  • Organizer: 日本泌尿器科学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2015-04-18