Molecular mechanisms of left-right asymmetric morphogenesis in visceral organs and limb

2012 Fiscal Year Final Research Report

• Project/Area Number: 22770215
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Developmental biology
• Research Institution: Osaka University
• Principal Investigator: SHIRATORI Hidetaka 大阪大学, 生命機能研究科, 准教授 (90362590)
• Project Period (FY): 2010 – 2012
• Keywords: 発生・分化 / 左右軸 / 器官形成 / Pitx2 / Fgf10

Research Abstract

About left-right asymmetric morphogenesis in visceral organs and limb, I discovered the following molecular mechanisms:
（1）Endocardium, which receives Fgf signals, has important role in morphogenesis of heart outflow tract.
（2）Morphogenesis of heart outflow tract involves several Fgf factors in addition to Fgf10.
（3）Expression of Pitx2is initiated in left lateral plate mesoderm, and also begins at paraxial mesoderm cells in the limb bud.
(4)Cell proliferation rate of Pitx2-expressing cells in dorso-ventral region of left limb is different between wild type and Pitx2mutant embryos. Pitx2 inhibits cell proliferation in these cells.

Research Products

• [Journal Article] Asymmetric distribution of dynamic calcium signals in the node of mouse embryo during left-right axis formation (2013)
  • Author(s): Takao D, Nemoto T, Abe T, Kiyonari H, Kajiura-Kobayashi H, Shiratori H, Nonaka S
  • Journal Title: Dev Biol Volume: 376(1):23-30
  • DOI: doi:10.1016/j.ydbio.2013.01.018
  • Peer Reviewed
• [Journal Article] Cilia at the Node of Mouse Embryos Sense Fluid Flow for Left-Right Determination via Pkd2 (2012)
  • Author(s): Yoshiba S, Shiratori H, Kuo IY, Kawasumi A, Shinohara K, Nonaka S, Asai Y, Sasaki G, Belo JA, Sasaki H, Nakai J, Dworniczak B, Ehrlich BE, Pennekamp P, Hamada H
  • Journal Title: Science Volume: 338(6104):226-3
  • DOI: doi:10.1126/science.1222538
  • Peer Reviewed
• [Journal Article] Two rotating cilia in the node cavity are sufficient to break left-right symmetry in the mouse embryo (2012)
  • Author(s): Shinohara K, Kawasumi A, Takamatsu A, Yoshiba S, Botilde Y, Motoyama N, Reith W, Durand B, Shiratori H, Hamada H
  • Journal Title: Nat Commun Volume: 3:622
  • DOI: doi:10.1038/ncomms1624
  • Peer Reviewed
• [Journal Article] Left-right asymmetry in the level of active Nodal protein produced in the node is translate into left-right asymmetry in the lateral plate of mouse embryos (2011)
  • Author(s): Kawasumi A, Nakamura T, Iwai N, Yashiro K, Saijoh Y, Belo JA, Shiratori H, Hamada H
  • Journal Title: Dev Biol. Volume: 353(2):321-30
  • DOI: doi:10.1242/dev.063966
  • Peer Reviewed
• [Journal Article] Characterization of Pitx2c expression in the mouse heart using a reporter transgene (2011)
  • Author(s): Furtado MB, Biben C, Shiratori H, Hamada H, Harvey RP
  • Journal Title: Dev Dyn Volume: 240(1):195-203
  • DOI: doi:10.1016/j.ydbio.2011.03.009
  • Peer Reviewed
• [Journal Article] Dysregulation of the PDGFRA gene causes inflow tract anomalies including TAPVR: integrating evidence from human genetics and model organisms (2010)
  • Author(s): Bleyl SB, Saijoh Y, Bax NA, Gittenberger-de Groot AC, Wisse LJ, Chapman SC, Hunter J, Shiratori H, Hamada H, Yamada S, Shiota K, Klewer SE, Leppert MF, Schoenwolf GC
  • Journal Title: Human Molecular Genetics Volume: 19(7) Pages: 1286-1301
  • DOI: doi:10.1002/dvdy.22492
  • Peer Reviewed
• [Presentation] 器官の左右非対称性形成の分子機構 (2013)
  • Author(s): 白鳥秀卓
  • Organizer: 第153回日本獣医学会学術集会
  • Place of Presentation: 大宮ソニックシティ(埼玉県)
  • Year and Date: 2013-03-27
• [Presentation] マウスの左右非対称な器官形成機構 (2011)
  • Author(s): 白鳥秀卓
  • Organizer: 第151回日本獣医学会学術集会
  • Place of Presentation: 東京農工大学
  • Year and Date: 2011-03-30
• [Remarks]
  • URL: http://www.fbs.osaka-u.ac.jp/labs/hamada/