Roles of Rac1 during limb development

2009 Fiscal Year Final Research Report

• Project/Area Number: 20791361
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional basic dentistry
• Research Institution: Showa University
• Principal Investigator: YAMADA Atsushi Showa University, 歯学部・口腔生化学教室, 講師 (50407558)
• Research Collaborator: KAMIJO Ryutaro 昭和大学, 歯学部・口腔生化学教室, 教授 (70233939) ; SUZUKI Dai 昭和大学, 歯学部・口腔生化学教室, 大学院生
• Project Period (FY): 2008 – 2009
• Keywords: 遺伝子 / 細胞・組織 / 発生・分化 / シグナル伝達

Research Abstract

To investigate the physiological functions of Rac1, a member of the small Rho GTPase family, we generated Rac1 conditional knockout mice (Rac1 cKO mice) which are characterized by limb bud mesenchyme-specific inactivation of Rac1. Rac1 cKO mice had shorter body length and lower body weight as compared with control mice. Rac1 cKO mice also showed incomplete fusion of the sternum and cranium. The most striking feature of the Rac1 cKO mice fore- and hindlimbs was profound soft tissue syndactyly because of a complete absence of interdigital programmed cell death. Furthermore, the lack of interdigital programmed cell death and associated syndactyly was related to down-regulated gene expression of BMP-2 and BMP-7, which are known to promote apoptosis in the interdigital mesenchyme.

Research Products

• [Journal Article] Essential mesenchymal role of small GTPase Rac1 in interdigital programmed cell death during limb development (2009)
  • Author(s): Suzuki D, Yamada A, Amano T, Yasuhara R, Kimura A, Sakahara M, Tsumaki N, Takeda S, Tamura M, Nakamura M, Wada N, Nohno T, Shiroishi T, Aiba A, Kamijo R
  • Journal Title: Dev. Biol 335 Pages: 396-406
  • Peer Reviewed
• [Journal Article] Osteoclast differentiation induced by synthetic octacalcium phosphate through RANKL expression in osteoblasts (2009)
  • Author(s): Takami M, Mochizuki A, Yamada A, Tachi K, Zhao B, Miyamoto Y, Anada T, Honda Y, Inoue T, Nakamura M, Suzuki O, Kamijo R
  • Journal Title: Tissue Eng 15 Pages: 3991-4000
  • Peer Reviewed
• [Journal Article] Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis (2009)
  • Author(s): Zhao B, Takami M, Yamada A, Wang X, Koga T, Hu X, Tamura T, Ozato K, Choi Y, Ivashkiv LB, Takayanagi H, Kamijo R
  • Journal Title: Nat. Med 15 Pages: 1066-71
  • Peer Reviewed
• [Journal Article] IFN-・ down-regulates Secretoglobin 3A1 gene expression (2009)
  • Author(s): Yamada A, Suzuki D, Miyazono A, Oshima K, Kamiya A, Zhao B, Takami M, Donnelly RP, Itabe H, Yamamoto M, Kimura S, Kamijo R
  • Journal Title: Biochem. Biophys. Res. Commun 379 Pages: 964-968
  • Peer Reviewed
• [Journal Article] Oncostatin M regulates Secretoglobin 3A1 and 3A2 expression in a bidirectional manner (2009)
  • Author(s): Tomita T, Yamada A, Miyakoshi M, Kido T, Sheikh F, Srisodsai A, Miyajima A, Donnelly RP, Kimura S
  • Journal Title: Am. J. Respir. Cell Mol. Biol 40 Pages: 620-630
  • Peer Reviewed
• [Journal Article] Generation of Rac1 conditional mutant mice by Cre/loxP system (2009)
  • Author(s): Suzuki D, Yamada A, Amano T, Kimura A, Yasuhara R, Sakahara M, Tamura M, Tsumaki N, Takeda S, Nakamura M, Shiroishi T, Aiba A, Kamijo R
  • Journal Title: New Frontiers in Neuroscience Pages: 175-178
• [Journal Article] 四肢・骨格形成における低分子量Gタンパク質Rac1の役割 (2009)
  • Author(s): 鈴木大、安原理佳、山田篤
  • Journal Title: 口腔組織培養学会誌 18巻 Pages: 21-27
• [Journal Article] Characterization of synovial cell clones isolated from rheumatoid arthritis patients: possible involvement of TNF-・ in reduction of osteoproteger in in synovium (2008)
  • Author(s): Zhao B, Takami M, Miyamoto Y, Suzawa T, Yamada A, Mochizuki A, Yasuhara R, Wang X, Inoue T, Namiki O, Sakamoto K, Kamijo R
  • Journal Title: Cytokine 41 Pages: 61-70
  • Peer Reviewed
• [Presentation] 低分子量Gタンパク質Rac1による中枢性骨代謝制御機構の解析 (2010)
  • Author(s): 山田篤, 鈴木大, 松本貴志, 影山晴秋, 今井元, 荒田悟, 馬場一美, 塩田清二, 饗場篤, 上條竜太郎
  • Organizer: 昭和大学共同研究平成21年度研究成果発表会
  • Place of Presentation: 東京
  • Year and Date: 20100300
• [Presentation] Essential role of Rac1 during limb development (2009)
  • Author(s): Suzuki D, Yamada A, Amano T, Yasuhara R, Kimura A, Sakahara M, Tsumaki N, Takeda S, Tamura M, Nakamura M, Shiroishi T, Aiba A, Kamijo R
  • Organizer: American Society for Bone & Mineral Research (ASBMR) 31st Annual Meeting
  • Place of Presentation: Denver Colorado, USA
  • Year and Date: 20090900
• [Presentation] GremlinはBMP-2による骨芽細胞分化を制御する (2009)
  • Author(s): 鈴木大, 山田篤, 高見正道, 須澤徹夫, 宮本洋一, 上條竜太郎
  • Organizer: 第27回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20090700
• [Presentation] 低分子量Gタンパク質Rac1による中枢性骨代謝制御機構の解析 (2009)
  • Author(s): 山田篤, 鈴木大, 松本貴志, 影山晴秋, 今井元, 荒田悟, 馬場一美, 塩田清二, 饗場篤, 上條竜太郎
  • Organizer: 昭和大学共同研究平成20年度研究成果発表会
  • Place of Presentation: 東京
  • Year and Date: 20090300
• [Presentation] BMP活性制御物質の探索とその機能解析 (2009)
  • Author(s): 鈴木大, 山田篤, 松本貴志, 趙宝紅, 高見正道, 須澤徹夫, 宮本洋一, 馬場一美, 上條竜太郎
  • Organizer: 昭和大学歯学部口腔癌包括的研究センター平成20年度公開シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 20090300
• [Presentation] Essential role of small GTPase Rac1 during limb development (2009)
  • Author(s): Suzuki D, Yamada A, Amano T, Yasuhara R, Kimura A, Sakahara M, Tsumaki N, Takeda S, Tamura M, Nakamura M, Shiroishi T, Aiba A, Kamijo R
  • Organizer: 2nd Joint Meeting of the International Bone & Mineral Society and the Australian & New Zealand Bone & Mineral Society (IBMS-ANZBMS
  • Place of Presentation: Sydney, Australia
  • Year and Date: 20090300
• [Presentation] Rac1は四肢形成に必須である (2008)
  • Author(s): 鈴木大, 山田篤, 天野孝紀, 木村文子, 安原理佳, 妻木範行, 竹田秀, 田村勝, 中村雅典, 城石俊彦, 饗場篤, 上條竜太郎
  • Organizer: 第31回日本分子生物学会年会第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20081200
• [Presentation] Rac1は四肢形成に必須である (2008)
  • Author(s): 鈴木大, 山田篤, 天野孝紀, 木村文子, 安原理佳, 妻木範行, 竹田秀, 田村勝, 中村雅典, 城石俊彦, 饗場篤, 上條竜太郎
  • Organizer: 第45回日本口腔組織培養学会
  • Place of Presentation: 塩尻
  • Year and Date: 20081100
• [Presentation] 低分子量Gタンパク質Rac1は四肢形成に必須である (2008)
  • Author(s): 鈴木大, 山田篤, 木村文子, 安原理佳, 妻木範行, 竹田秀, 松本貴志, 馬場一美, 中村雅典, 饗場篤, 上條竜太郎
  • Organizer: 第26回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20081000
• [Presentation] Rac1 controls interdigital programmed cell death in limb buds (2008)
  • Author(s): Suzuki D, Yamada A, Yasuhara R, Tsumaki N, Nakamura M, Kamijo R
  • Organizer: The 1st Showa International Symposium for Life Science 5th Annual Meeting
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 20080900
• [Presentation] 低分子量Gタンパク質Rac1は四肢形成に必須である (2008)
  • Author(s): 鈴木大, 山田篤, 安原理佳, 木村文子, 妻木範行, 竹田秀, 中村雅典, 饗場篤, 上條竜太郎
  • Organizer: 第73回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 20080700
• [Presentation] Essential role of small GTPase Rac1 in limb development (2008)
  • Author(s): Suzuki D, Yamada A, Yasuhara R, Nakamura M, Kamijo R
  • Organizer: 第28回昭和歯学会総会
  • Place of Presentation: 東京
  • Year and Date: 20080600