Establishment of cell polarity by interactions between Wnt and PCP factors.

• Project/Area Number: 18K14720
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: National Institute for Basic Biology
• Principal Investigator: Mii Yusuke 基礎生物学研究所, 分子発生学研究部門, 助教 (70634129)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Xenopus / アフリカツメガエル / Wnt / モルフォゲン / 平面細胞極性 / PCP / イメージング / 超解像イメージング / ヘパラン硫酸

Outline of Final Research Achievements

Planar cell polarity is the directionaly of cells within a tissue plain, which is widely conserved among animals. A family of secreted signaling proteins, Wnt has been considered as a directional cue for PCP, supposedly by forming a concentration gradient as a morphogen. However, this model is not directly examined because visualization of Wnt ligands are still lacking. In this study, we found that a subtype of Wnt proteins involved in PCP did not show graded distributions, based on visualization of Wnt proteins. Furthermore, we found that core PCP components, which are essential for PCP formation, are involved in the distribution of the Wnt protein.

Academic Significance and Societal Importance of the Research Achievements

これまで、分泌性のシグナル蛋白質であるWntは濃度勾配によって位置情報を与える物質「モルフォゲン」の一種と捉えられており、この文脈にそって、組織平面内の細胞の方向性である「平面細胞極性」もWntの濃度勾配によって向きが揃えられていると考えられてきた。しかし、本研究からWnt蛋白質の分布が必ずしも濃度勾配的ではないことが判明し、さらに平面細胞極性の必須因子であるコアPCP因子はWntの分布に関与することが示された。これは従来のモルフォゲンの範疇にとどまらないWntの作用機序に対する理解を大きく前進させるものである。

Research Products

• [Journal Article] Quantitative analyses reveal extracellular dynamics of Wnt ligands in Xenopus embryos (2020)
  • Author(s): Mii Yusuke、Nakazato Kenichi、Pack Chan-Gi、Sako Yasushi、Mochizuki Atsushi、Takada Shinji、Taira Masanori
  • Journal Title: bioRxiv Volume: -
  • DOI: 10.1101/2020.02.20.957860
  • NAID: 120007041648
  • Open Access / Int'l Joint Research
• [Journal Article] Assembly of protein complexes restricts diffusion of Wnt3a proteins (2018)
  • Author(s): Takada, R., Mii, Y., Krayukhina, E., Maruyama, Y., Mio, K., Sasaki, Y., Shinkawa, T., Pack, C.-G., Sako, Y., Sato, C., Uchiyama, S., Takada, S.
  • Journal Title: Commun. Biol. Volume: 1 Issue: 1 Pages: 165-165
  • DOI: 10.1038/s42003-018-0172-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Local and mutual regulations between Wnt and planar cell polarity components propagate global coordination of the planar cell polarity. (2019)
  • Author(s): 三井優輔、高田律子、松山誠、高田慎治
  • Organizer: 第52回日本発生生物学会大会
• [Presentation] Two types of heparan sulfate clusters differently regulate Wnt distribution and signaling in Xenopus embryos. (2019)
  • Author(s): Yusuke Mii, Takayoshi Yamamoto, Ritsuko Takada, Shuji Mizumoto, Makoto Matsuyama, Shuhei Yamada, and Masanori Taira & Shinji Takada
  • Organizer: 11th International Conference on Proteoglycans
  • Int'l Joint Research
• [Presentation] How does Wnt11 direct the planar cell polarity? (2019)
  • Author(s): Yusuke Mii
  • Organizer: 119th International Titisee Conference
  • Int'l Joint Research / Invited
• [Presentation] Local and mutual regulations between Wnt and planar cell polarity propagate global coordination of cell polarity throughout the tissue. (2018)
  • Author(s): 三井 優輔
  • Organizer: 第70回日本細胞生物学会・第51回日本発生生物学会合同大会
  • Invited
• [Remarks] 分子発生学研究部門
  • URL: https://www.nibb.ac.jp/cib2/
• [Remarks] researchmap 三井 優輔
  • URL: https://researchmap.jp/miiy
• [Remarks] 分子発生学研究部門
  • URL: http://www.nibb.ac.jp/sections/developmental_biology/takada/
• [Remarks] 分子発生学研究部門（高田研究室）
  • URL: http://www.nibb.ac.jp/cib2/