Role of Daple in the inner ear morphogenesis

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K16887
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Osaka University
• Principal Investigator: Ozono Yoshiyuki 大阪大学, 医学系研究科, 特任研究員 (10724768)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 内耳 / 平面細胞極性 / 細胞骨格 / 難聴

Outline of Final Research Achievements

The V-shaped arrangement of hair bundles on cochlear hair cells is critical for auditory sensing. However, regulation of hair bundle arrangements has not been fully understood. In the present study, we found that Daple(Ccdc88c)－/－ mice exhibited hearing disturbances over a broad frequency range through auditory brainstem response testing. Consistently, distorted patterns of hair bundles were detected in almost all regions, more typically in the basal region of the cochlear duct. In Daple－/－ mice, apical microtubules were irregularly aggregated, and the number of microtubules attached to plasma membranes was decreased. Similar phenotypes were manifested upon nocodazole treatment in a wild type cochlea culture without affecting the microtubule structure of the kinocilium. These results indicate critical role of Daple in hair bundle arrangement through the orchestration of apical microtubule distribution, and thereby in hearing.

Free Research Field

耳鼻咽喉科

Academic Significance and Societal Importance of the Research Achievements

胚の発生、器官形成、生体恒常性維持には、細胞内、細胞間の極性を正しく決めるメカニズムが重要である（平面細胞極性planar cell polarity :PCP）。本研究は蝸牛のPCPにおけるDaple(Ccdc88c)の役割を明らかにし、蝸牛PCP異常下での聴覚障害や、生体におけるPCP調整のメカニズムを解明する一助になる成果を報告した。