Regulation of cell proliferation by Wnt signaling and apical-basal polarity in lung

• Project/Area Number: 24770186
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: Osaka University
• Principal Investigator: FUMOTO Katsumi 大阪大学, 医学(系)研究科(研究院), 助教 (40467783)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 上皮細胞 / 頂底極性 / 細胞増殖 / 組織構築 / wnt / 肺 / 分岐形態形成 / 上皮単独培養 / 期間培養 / Wntシグナル / 上皮組織 / 接着

Research Abstract

In this study, we aim to elucidate the mechanism for lung branching morphogenesis which is mediated by Wnt signaling. We have already generated three dimensional culture system of lung epithelium. By using this, we treated the epithelium with CHIR99021, an agonist for beta-catenin pathway or transduced lentiviruses that express Wnt2, a typical ligand for beta-catenin dependent pathway. CHIR or Wnt2 promoted branching morphogenesis. Activation of beta-catenin pathway promoted apical constriction provably through enhanced localization of atypical PKCzeta (aPKCzeta), a critical regulator of apical and basal polarity, to apical membrane. In addition, aPKCzeta inhibitor showed the defect in branching morphogenesis and apical constriction. In conclusion, we found that beta-catenin pathway maintains distal progenitor and is required for branching morphogenesis provably through apical targeting of aPKCzeta and apical constriction.

Research Products

• [Journal Article] Wnt5a signaling promotes apical and basolateral polarization of single epithelial cells (2013)
  • Author(s): Gon H, Fumoto K, Ku Y, Matsumoto S, Kikuchi A
  • Journal Title: Mol. Biol. Cell Volume: 23 Pages: 3764-7374
  • Peer Reviewed
• [Journal Article] ALS-associated mutations in FUS disrupt the axonal distribution and function of SMN (2013)
  • Author(s): Groen EJ, Fumoto K, Blokhuis AM, Engelen-Lee J, Zhou Y, van den Heuvel DM, Koppers M, van Diggelen F, van Heest J, Demmers JA, Kirby J, Shaw PJ, Aronica E, Spliet WG, Veldink JH, van den Berg LH, Pasterkamp RJ
  • Journal Title: Hum. Mol. Genet. Volume: 22 Pages: 3690-3704
  • Peer Reviewed
• [Journal Article] Wnt5a signaling promotes apical and basolateral polarization of single epithelial cells. (2013)
  • Author(s): Gon, H., Fumoto, K., Ku, Y., Matsumoto, S., and Kikuchi, A.
  • Journal Title: Mol. Biol. Cell. Volume: 24 Issue: 23 Pages: 3764-3774
  • DOI: 10.1091/mbc.e13-07-0357
  • Peer Reviewed
• [Journal Article] "ALS-associated mutations in FUS disrupt the axonal distribution and function of SMN." (2013)
  • Author(s): Groen EJ, Fumoto K, Blokhuis AM, Engelen-Lee J, Zhou Y, van den Heuvel DM, Koppers M, van Diggelen F, van Heest J, Demmers JA, Kirby J, Shaw PJ, Aronica E, Spliet WG, Veldink JH, van den Berg LH, Pasterkamp RJ.
  • Journal Title: Human Molecular Genetics Volume: 22 Issue: 18 Pages: 3690-3704
  • DOI: 10.1093/hmg/ddt222
  • Peer Reviewed
• [Journal Article] Wnt5a signaling controls cytokinesis by correctly positioning ESCRT-III at the midbody. (2012)
  • Author(s): Fumoto, K.*, Kikuchi, K.*, Gon, H., and Kikuchi, A. (*: equal contribution)
  • Journal Title: Journal of Cell Science Volume: 125 Pages: 4822-4832
  • DOI: 10.1242/jcs.108142
  • Peer Reviewed
• [Journal Article] Wnt5a signaling controls cytokinesis by positioning ESCRT-III to the proper site at the midbody (2011)
  • Author(s): Fumoto K, Kikuchi K, Gon H, and Kikuchi A
  • Journal Title: J. Cell Sci. Volume: 125 Pages: 4822-4832
  • Peer Reviewed
• [Presentation] 肺分岐形態形成におけるWntシグナルによる分裂軸制御機構及び生理的意義 (2013)
  • Author(s): 麓勝己
  • Organizer: 第36回日本分子生物学会
  • Year and Date: 2013-12-04
• [Presentation] Regulation of lung branching morphogenesis by Wnt signaling and mitotic cells (2013)
  • Author(s): 麓勝己
  • Organizer: 第1回若手研究フォーラム
  • Place of Presentation: 大阪大学
  • Year and Date: 2013-09-26
• [Presentation] Regulation of lung branching morphogenesis by growth factor signaling (2013)
  • Author(s): 麓勝己
  • Organizer: 第一回epithelial tubulology国際会議
  • Place of Presentation: 北海道大学
  • Year and Date: 2013-06-23
• [Presentation] Regulation of lung branching morphogenesis by Wnt signaling and mitotic cells (2013)
  • Author(s): 麓 勝己
  • Organizer: 第１回若手研究フォーラム
  • Place of Presentation: 大阪大学銀杏会館
• [Presentation] 肺分岐形態形成におけるWnt シグナルによる分裂軸制御機構及び生理的意義 (2013)
  • Author(s): 麓 勝己、菊池 章
  • Organizer: 第３６回分子生物学会
  • Place of Presentation: 神戸国際展示場
• [Presentation] Regulation of cytokinesis by Wnt5a signaling (2012)
  • Author(s): Katsumi Fumoto
  • Organizer: 日本分子生物学会
  • Place of Presentation: マリンメッセ福岡
• [Book] Wnt signaling (2014)
  • Author(s): Kikuchi A., Matsumoto S., Fumoto K., Sato A
  • Total Pages: 472
  • Publisher: John Wiley and Sons, Inc.
• [Book] Wnt Signaling (Chaper 8) (2014)
  • Author(s): Kikuchi, A., Matsumoto, S., Fumoto, K., and Sato, A.
  • Total Pages: 472
  • Publisher: John Wiley and Sons, Inc.