Spatio-temporal change of Atoh1 expression in developing cochlear prosensory epithelium visualized by 3D real-time imaging.

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K11179
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kyoto University of Advanced Science (2019); Kyoto University (2016-2018)
• Principal Investigator: Tateya Tomoko 京都先端科学大学, 健康医療学部, 准教授 (10512311)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 有毛細胞 / 蝸牛感覚上皮 / Atoh1

Outline of Final Research Achievements

During cochlear development, hair cells (HCs) and supporting cells differentiate in the prosensory domain to form the organ of Corti, but how one row of inner HCs (IHCs) and three rows of outer HCs (OHCs) are organized is not well understood. We investigated the process of HC induction by monitoring Atoh1 expression in cochlear explants of Atoh1-EGFP knock-in mouse embryos and showed that only the cells that express Atoh1 over a certain threshold are selected for HC fate determination. HC induction initially occurs at the medial edge of the prosensory domain to form IHCs and subsequently at the lateral edge to form OHCs, while Hedgehog signaling maintains a space between IHCs and OHCs, leading to formation of the tunnel of Corti. These results reveal dynamic Atoh1 expression in HC fate control and suggest that multi-directional signals regulate OHC induction, thereby organizing the prototype of the organ of Corti.

Free Research Field

耳鼻咽喉科学

Academic Significance and Societal Importance of the Research Achievements

治療法のない難聴の殆どが蝸牛有毛細胞の障害を原因とすることから、聴覚再生に向けた研究の多くが有毛細胞の再生を目的としてきた。蝸牛の内有毛細胞と外有毛細胞は機能も異なり、内有毛細胞が聴覚情報を中枢に伝え、外有毛細胞は聴覚情報の増幅器として機能する。蝸牛の有毛細胞は、機能的に分化し高度の規則性をもって配列する細胞であるだけに、それをin vitroで作り出すことは現時点では困難であり、聴覚再生研究における次なるマイルストーンとも言える。本研究は、内有毛細胞と外有毛細胞の分化メカニズムを解明するものであり、この結果はさらなる聴覚再生研究に寄与できると考えられる