Elucidating the function of primary cilia during maxillofacial development: In terms of signal pathway crosstalk

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K10092
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Niigata University
• Principal Investigator: Kawasaki Maiko 新潟大学, 医歯学系, 准教授 (40584587)
• Co-Investigator(Kenkyū-buntansha): 前田 健康 新潟大学, 医歯学系, 教授 (40183941) ; 大峡 淳 新潟大学, 医歯学系, 教授 (40266169) ; 川崎 勝盛 新潟大学, 医歯学系, 助教 (40529640)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: SHH / WNT / 一次繊毛

Outline of Final Research Achievements

In this study, the interaction between SHH and WNT signaling pathways was analyzed using morphological and molecular biological techniques in transgenic mice in which both SHH and WNT signaling pathways functioning within the primary cilia were regulated. This revealed the function of primary cilia during the development of the maxillofacial region. Transgenic mice in which both SHH and WNT were regulated showed cleft palate, abnormal tooth number, abnormal tooth morphology, and delayed tooth formation. However, their phenotypes approximated either phenotype of mice in which each was controlled alone. The phenotypes of the mice created by this study were extremely severe morphological abnormalities in the maxillofacial region, indicating that the SHH and WNT signaling pathways each play a very important role as regulators of morphogenesis of the maxillofacial region.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

一次繊毛のこれまでの役割である、SHHやWNTによるシグナル伝達および細胞小器官の 合成と維持に加え、本研究で明らかにされる新たな各シグナル間のクロストーク機構の解明より、一次繊毛のより詳細な機能解明が可能となり、歯学のみならず広範な基礎生物学の進展に寄与する。さらに、本申請研究は一次繊毛の機能解明だけでなく、SHH、WNTシグナル経路の異常を原因とする各種先天異常の原因の解明、治療法の開発に貢献できる。これまで対症療法しかなかった繊毛病治療にシグナル経路サイドからの遺伝子治療や予防薬の開発という新しい視点を提供することができる。患者に侵襲の少ない治療を提案することが可能となる。