Study on the formation and arrangement of the inner ear sensory epithelium responsible for hearing and balance.

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K07273
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Jichi Medical University
• Principal Investigator: Sato Shigeru 自治医科大学, 医学部, 准教授 (70306108)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 内耳形成 / プラコード / 耳胞 / ホメオボックス遺伝子 / エンハンサー / ゲノム編集 / 行動異常 / 有毛細胞

Outline of Final Research Achievements

The mammalian inner ear is one of the most elaborate sensory organs. During development, the transcription factor SIX1 acts in the right place at the right time to regionalise the otic vesicle, differentiate the cells and facilitate the organ formation. The present study was undertaken to elucidate the regulatory mechanisms of Six1 gene expression. Based on the analysis of the chromatin structure of mouse inner ear hair cells, among others, three candidate enhancers that activate transcription were identified. The upstream signalling molecule WNT and the transcription factor FOX were identified. The presence of SIX1 binding sites within the enhancers was also suggested to allow for the continuous expression of Six1. Mice lacking two major enhancers showed severe behavioral abnormalities, a small inner ear and the absence of a normal morphology of the cochlea.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

哺乳類の内耳は最も精巧な感覚器の1つであり、聴覚と平衡覚を司る。本研究は、内耳の形成に不可欠なSix1遺伝子に注目した研究を進めた。その結果、有毛細胞でSix1を発現させるスイッチの候補、上流ではたらくシグナルと転写因子、Six1が内耳形成過程で発現を続ける仕組みの一端も明らかにできた。２つの重要なスイッチを欠失するマウスは、行動と内耳構造が異常となり、鰓耳腎症候群の新たなモデルになることもわかった。本研究は内耳形成、難聴の理解、再生医療に役立つ。