Elucidating the mechanism of the Wnt/PCP signaling pathway by the genome editing technology

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07054
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Kumamoto University
• Principal Investigator: Kikuchi Koji 熊本大学, 大学院生命科学研究部(医), 講師 (70457290)
• Co-Investigator(Renkei-kenkyūsha): TANAKA Tsubasa 熊本大学, 発生医学研究所, 助教 (00392027)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: Wnt5aシグナル経路 / 微小管 / 微小管結合タンパク質 / Dishevelled / キネシン / 細胞接着 / 細胞運動 / 平面内細胞極性

Outline of Final Research Achievements

Wnt5a signaling through a β-catenin-independent pathway promotes microtubule (MT) remodeling during cell-substrate adhesion, cell migration, and planer cell polarity (PCP) formation, all of which are essential features of tissue morphogenesis. Although Wnt5a signaling and MT remodeling are known to form an interdependent regulatory loop, the underlying mechanism remains unknown. Here we show that Map7/7D1 cooperate with Kif5b to coordinate a feedback loop between Dvl dynamics and MT remodeling in the Wnt5a signaling pathway, and that the role of Map7/7D1 family proteins in Dvl/Dsh localization is evolutionarily conserved.
As a methodological highlight, we adapted a CRISPR-Cas9-mediated genome editing technology to generate knock-in HeLa cells and fly strains. As the overexpression of Map7/7D1 family proteins is reported to induce aberrant MT bundling, this strategy allowed us to reliably analyze behaviors of endogenous Map7/7D1 family proteins in cells and tissues.

Free Research Field

細胞生物学、分子生物学、生化学