Analysis of the molecular mechanism for the determination of cell fate and the tissue organization with Notch signaling

• Project/Area Number: 19390115
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tokai University
• Principal Investigator: HOZUMI Katsuto Tokai University, 医学部, 准教授 (30246079)
• Co-Investigator(Kenkyū-buntansha): ANDO Kiyoshi 東海大学, 医学部, 教授 (70176014) ; IMAI Kenji 東海大学, 医学部, 教授 (70193646)
• Co-Investigator(Renkei-kenkyūsha): ANDO Kiyoshi
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2008: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000); Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: Notch / Notchリガンド / 細胞系譜 / 胸腺 / 骨髄 / Jaggedl / 骨芽細胞 / 膵臓

Research Abstract

生体防御反応にて中心的な役割を果たすT細胞は、胸腺にて分化成熟し、末梢リンパ組織に供給される。T細胞は胸腺に依存して分化するが、その分子基盤については明らかでなかった。本研究では、T細胞分化に必須のNotchシグナルが、胸腺分化環境を担う胸腺上皮細胞上に発現するNotchリガンド:Dll4を介して、胸腺に移動してきた造血未分化細胞に付与され、T細胞への系列決定が成されることを明らかにした。

Research Products

• [Journal Article] Delta-like 4 is indispensable in thymic environment specific for T cell development. (2008)
  • Author(s): Hozumi, K., Mailhos, C., Negishi, N., Hirano, K., Yahata, T., Ando, K., Zuklys, S., Hollander, G. A., Shima, D. T. and Habu, S.
  • Journal Title: J. Exp. Med. 205 Pages: 2507-2513
  • NAID: 40016715345
  • Peer Reviewed
• [Journal Article] Notch signaling is necessary for GATA3 function in the initiation of T cell development. (2008)
  • Author(s): Hozumi, K., Negishi, N., Tsuchiya, I., Abe, N., Hirano, K., Suzuki, D., Yamamoto, M., Engel, J. D. and Habu, S.
  • Journal Title: Eur. J. Immunol. 38 Pages: 977-985
  • Peer Reviewed
• [Journal Article] Expression of Delta-like 1 in the splenic non-hematopoietic cells is essential for marginal zone B cell development. (2008)
  • Author(s): Sheng, Y., Yahata, T., Negishi, N., Nakano, Y., Habu, S., Hozumi, K. and Ando, K.
  • Journal Title: Immunol. Lett. 121 Pages: 33-37
  • Peer Reviewed
• [Journal Article] Delta-like 4 is indispensable in thymic environment specific for T cell development. (2008)
  • Author(s): Hozumi K., et al.
  • Journal Title: Journal of Experimental Medicine 205 Pages: 2507-2513
  • NAID: 40016715345
  • Peer Reviewed
• [Journal Article] Notch signaling is necessary for GATA3 function in the initiation of T cell development. (2008)
  • Author(s): Hozumi K., et al.
  • Journal Title: European Journal of Immunology 38 Pages: 977-985
  • Peer Reviewed
• [Journal Article] Selection of differentiating cells by different levels of Delta-like 1 among neural precursor cells in the developing mouse telencephalon. (2008)
  • Author(s): Kawaguchi D., et al.
  • Journal Title: Development 135 Pages: 3849-3858
  • Peer Reviewed
• [Journal Article] Expression of Delta-like 1 in the splenic non-hematopoietic cells is essential for marginal zone B cell development. (2008)
  • Author(s): Sheng Y., et al.
  • Journal Title: Immunology Letters 121 Pages: 33-37
  • Peer Reviewed
• [Journal Article] Specific Jaggedl-signal from bone marrow microenvironment is required for endothelial progenitor cell development for neovascularization. (2008)
  • Author(s): Kwon SM., et al.
  • Journal Title: European Journal of Immunology 118 Pages: 157-165
  • Peer Reviewed
• [Journal Article] Role of the Notch ligand Deltal in embryonic and adult mouse epidermis. (2008)
  • Author(s): Estrach S., et al.
  • Journal Title: European Journal of Immunology 128 Pages: 825-832
  • Peer Reviewed
• [Journal Article] Role of the Notch ligand Delta 1 in embryonic and adult mouse epidermis (2008)
  • Author(s): Estrach, S., et al.
  • Journal Title: J. Invest. Dermatol. 128 Pages: 825-832
  • Peer Reviewed
• [Journal Article] Mastermind-1 is required for Notch signal-dependent steps in lymphocyte development in vivo. (2007)
  • Author(s): Oyama, T., Harigaya, K., Muradil, A., Hozumi, K., Habu, S., Iwama, A., Oguro, H., Matsuno, K., Sakamoto, R., Sato, M., Yoshida, N. and Kitagawa, M.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 104 Pages: 9764-9769
  • Peer Reviewed
• [Journal Article] Mastermind-1 is required for Notch signal-dependent steps in lymphocyte development in vivo (2007)
  • Author(s): Oyama, T., et al.
  • Journal Title: Proc. Natl. Acad. Sd. USA 104 Pages: 9764-9769
  • Peer Reviewed
• [Presentation] 胸腺分化環境要因としてのNotchリガンド:Dll4の役割 (2008)
  • Author(s): 穂積勝人
  • Organizer: 、第31回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] Notch ligandの機能的差異における転写因子LRFの役割の検証 (2008)
  • Author(s): 阿部奈津美
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] 胸腺分化環境要因としてのNotchリガンド : D114の役割 (2008)
  • Author(s): 穂積勝人
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-11
• [Presentation] Notch 1igandの機能的差異における転写因子LRFの役割の検証 (2008)
  • Author(s): 阿部奈津美
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-11
• [Presentation] 胸腺分化環境要因としてのDll4の役割 (2008)
  • Author(s): 穂積勝人
  • Organizer: 第38回日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] DN/DP胸腺細胞分化におけるDll4の役割 (2008)
  • Author(s): 平野健一
  • Organizer: 第38回日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] 胸腺環境要因としてのD114の役割 (2008)
  • Author(s): 穂積勝人
  • Organizer: 第38回日本免疫学会総会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-12-02
• [Presentation] DN/DP胸腺細胞分化におけるD114の役割 (2008)
  • Author(s): 平野健一
  • Organizer: 第38回日本免疫学会総会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-12-02
• [Presentation] Dll4 expressed on thymic epithelial cells s required for T cell development in the thymus. (2007)
  • Author(s): 穂積勝人
  • Organizer: シンポジウム、第37回日本免疫学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] Jagged1がDll4と同等のシグナルを伝達する時、造血前駆細胞にT細胞分化は誘導されるか (2007)
  • Author(s): 阿部奈津美
  • Organizer: 第37回日本免疫学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] Dll4 expressed on thymic epithelial cells is required for T cell development in the thymus (2007)
  • Author(s): Hozumi, K., et al.
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪
  • Year and Date: 2007-11-21