New challenge of control failure of palatal fusion as molecularly target TGF-B/Ras signal.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K17159
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Osaka University
• Principal Investigator: AOYAMA GOZO 大阪大学, 大学院歯学研究科, 招へい教員 (00838542)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 二次口蓋の癒合 / 口唇口蓋裂 / TGF-B / Rasシグナル経路

Outline of Final Research Achievements

It is known that various factors involved in the development of cleft lip and palate, in particular, abnormal dynamics of the palatal epithelium are greatly involved in the onset of cleft palate. We found that secondary palatal epithelial removal was inhibited by live imaging techniques of the palatine process epithelium in the Ras inhibitor group. Similarly, in stationary culture, palatal fusion was suppressed in the Ras inhibitor group, and E-cadherin and p63 were strongly expressed in the medial edge epithelium of the palatal fusion surface. In addition, focusing on RREB1, a downstream molecule of Ras signaling, the Rreb1 gene was specifically expressed in the medial edge epithelium of the palatal fusion surface, and palatine process fusion was suppressed in the Rreb1 knockdown group. We found that Ras signaling and Rreb1 genes are important factors for palatal fusion.

Free Research Field

組織発生学

Academic Significance and Societal Importance of the Research Achievements

本研究は口蓋突起上皮のライブイメージング技術を応用することで、TGF-β/Rasシグナル経路が口蓋突起癒合における細胞動態にどのような影響を及ぼしているかを解明し、Rasシグナル経路を制御するための標的分子を探索する新しい取り組みである。Rasシグナルの標的分子であるRREB1を用いた実験系を確立したことにより、口蓋突起癒合不全に特異性の高いTGF-β/Rasシグナル分子標的治療法の構築を進めていくことが可能になる。