The mechanisms of joint site determination

• Project/Area Number: 25870202
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General anatomy (including histology/embryology); General medical chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: HARADA MASAYO 東京医科歯科大学, 医歯(薬)学総合研究科, 助教 (80555756)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 関節 / 骨 / FGF

Outline of Final Research Achievements

The goal of this research was to explore the developmental mechanisms of bone and joint formaiton related to FGF signaling utilizing Elbow knee synostosis (Eks) mutant mice. We identified a missense mutation in the Fgf9 gene that is responsible for the Eks mutant phenotype, which includes elbow and knee joint synostosis and a thick and short long bones. This research suggested that 1)The expression of Sfrp2 and Noggin induced by supression of FGF signaling at the prospective elbow and knee joints is required for joint development. 2)Supression of FGF signaling at the prospective knee joint is required for compartmentalization of articular cavity and crucial ligament in knee joint. 3)FGF signaling is required for the pericondrium formation and might regulate thickness of long bones.

Research Products

• [Journal Article] Tissue-specific roles of FGF signaling in external genitalia development (2015)
  • Author(s): Harada M, Omori A, Nakahara C, Nakagata N, Akita K, Yamada G.
  • Journal Title: Developmental Dynamics Volume: - Issue: 6 Pages: 759-773
  • DOI: 10.1002/dvdy.24277
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Region-specific regulation of cell proliferation by FGF receptor signaling during the Wolffian duct development (2015)
  • Author(s): Okazawa M, Murashima A, Harada M, Nakagata N, Noguchi M, Morimoto M, Kimura T, Ornitz DM, Yamada G.
  • Journal Title: Developmental Biology Volume: 400 Pages: 139-147
  • Peer Reviewed
• [Journal Article] Disruption of the temporally regulated cloaca endodermal β-catenin signaling causes anorectal malformations (2014)
  • Author(s): Miyagawa S, Harada M, Matsumaru D, Tanaka K, Inoue C, Nakahara C, Haraguchi R, Matsushita S, Suzuki K, Nakagata N, Ng RC, Akita K, Lui VC, Yamada G.
  • Journal Title: Cell Death Differ. Volume: 21 Issue: 6 Pages: 990-997
  • DOI: 10.1038/cdd.2014.21
  • Peer Reviewed / Open Access
• [Journal Article] Dynamic intersection of the longitudinal muscle and external anal sphincter in the layered structure of the anal canal posterior wall (2013)
  • Author(s): Muro S, Yamaguchi K, Nakajima Y, Watanabe K, Harada M, Nimura A, Akita K.
  • Journal Title: Surg Radiol Anat. Volume: Nov 21 Issue: 6 Pages: 551-559
  • DOI: 10.1007/s00276-013-1228-8
  • Peer Reviewed
• [Presentation] 線維芽細胞増殖因子受容体（FGFR）シグナリングによる領域特異的なウォルフ管上細胞増殖の調節について (2014)
  • Author(s): 岡澤美佳、村嶋亜紀、原田理代、木村正、山田源
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 神奈川県横浜市パシフィコ横浜
  • Year and Date: 2014-11-27
• [Presentation] Bone morphogenetic protein (Bmp)シグナルは前立腺上皮細胞分化に必須である (2013)
  • Author(s): 大森晶子、宮川信一、荻野由紀子、原田理代、石井健一郎、杉村芳樹、山田源
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸
• [Presentation] Spatial arrangements of the muscle layers of the posterior wall of anal canal (2013)
  • Author(s): Akita K, Muro S, Watanabe K, Yamaguchi K, Nakajima Y, Harada M.
  • Organizer: European Joint Congress of Clinical Anatomy 2013
  • Place of Presentation: Lisbon
• [Presentation] Morphalogy of the perineal skeletal muscle revisited (2013)
  • Author(s): Akita K, Yamaguchi K, Muro S, Watanabe K, Harada M.
  • Organizer: 5th Internatilnal Symposion of Clinical and Applied Anatomy/ 1st Paneuropean Meeting of Anatomists
  • Place of Presentation: Graz