Investigation of G protein receptor signaling for regenerative medicine.

• Project/Area Number: 20590295
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: KATAOKA Hiroshi The Institute of Physical and Chemical Research, 幹細胞研究グループ, 客員研究員 (80455336)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: G蛋白 / Gi / RhoJ / 血管新生 / 百日咳毒素 / G蛋白受容体 / ES細胞 / 血管内皮 / 内皮細胞 / Es細胞

Research Abstract

To utilize G protein signaling apparatus in regenerative medicine roles of G protein signaling during embryonic development and angiogenesis were explored. We were able to obtain following results.
1. To inhibit Gi signaling in various cell types a mouse line that can express pertussi after removal of STOP cassette by Cre was developed. This line was used to block Gi signaling specifically in the vascular or nervous system. We found that Gi is critical for endocardial-mesenchymal transition in heart. In the nervous system Gi is required for neural tube closure in neuroepithelal cells. Ablation of Gi signaling in migrating neurons indicated the existence of important GPCRs in addition to CXCR4.
2. As a downstream effecter of G protein signaling we focused RhoJ. Knocking out RhoJ or endothelial-specific overexpression revealed that RhoJ is required for the endothelial morphology change.

Research Products

• [Journal Article] Sema3E-PlexinD1 signaling selectively suppresses disoriented angiogenesis in ischemic retinopathy in mice. (2011)
  • Author(s): Fukushima Y, Okada M, Kataoka H, Hirashima M, Yoshida Y, Mann F, Gomi F, Nishida K, Nishikawa S, Uemura A
  • Journal Title: J Clin Invest. 121(5) Pages: 1974-85
  • Peer Reviewed
• [Journal Article] Sema3E-PlexinD1 signaling activates endothelial RhoJ and selectively suppresses disoriented angiogenesis in ischemic retinopathy in mice (2011)
  • Author(s): Fukushima., et al
  • Journal Title: Journal of Clinical Investigation Volume: (in press)
  • Peer Reviewed
• [Journal Article] Local protease signaling contributes to neural tube closure in the mouse embryo. (2010)
  • Author(s): Camerer E, Barker A, Duong DN, Ganesan R, Kataoka H, Cornelissen I, Darragh MR, Hussain A, Zheng YW, Srinivasan Y, Brown C, Xu SM, Regard JB, Lin CY, Craik CS, Kirchhofer D, Coughlin SR
  • Journal Title: Dev Cell. 18(1) Pages: 25-38
  • Peer Reviewed
• [Journal Article] Local Protease Signaling Contributes to Neural Tube Closure in the Mouse Embryo (2010)
  • Author(s): Camerer, et.al.
  • Journal Title: Developmental Cell 18 Pages: 25-38
  • Peer Reviewed
• [Journal Article] Identification of a transient subpial neurogenic zone in the developing dentate gyrus and its regulation by Cxcl12 and reelin signaling. (2009)
  • Author(s): Li G, Kataoka H, Coughlin SR, Pleasure SJ
  • Journal Title: Development. 136(2) Pages: 327-35
  • Peer Reviewed
• [Journal Article] Identification of a transient subpial neurogenic zone in the developing dentate gyrus and its regulation by Cxcl12 and Reelin signaling
  • Author(s): Guangnan Li
  • Journal Title: Development
  • Peer Reviewed
• [Presentation] Development of Hematopoiesis explained (2010)
  • Author(s): 片岡宏
  • Organizer: Gordon Research Conference
  • Place of Presentation: ニューイングランド、米国
  • Year and Date: 2010-08-12
• [Presentation] Development of Hematopoiesis Explained (2010)
  • Author(s): Hiroshi Kataoka
  • Organizer: Gordon Research Conference
  • Place of Presentation: New England, MA, USA
  • Year and Date: 2010-08-12
• [Presentation] Etv2 induces lateral mesoderm from primitive mesoderm. (2010)
  • Author(s): 片岡宏
  • Organizer: 理研ケンブリッジCSCR合同セミナー
  • Place of Presentation: ケンブリッジ、英国
  • Year and Date: 2010-07-05
• [Presentation] Etv2 induces lateral mesoderm from primitive mesoderm. (2010)
  • Author(s): 片岡宏
  • Organizer: 幹細胞シンポジウム
  • Place of Presentation: 淡路
  • Year and Date: 2010-05-13
• [Remarks] ホームページ等