Dispensable role of Rac1 and Rac3 after cochlear hair cell specification

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  • Mohri Hiroaki
    Lab. of Mol. Pharmacol., Biosignal Research Center, Kobe Univ. Dept. of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural Univ. of Med. Dept. of Otolaryngology-Head and Neck Surgery, Red Cross Kyoto Daiichi Hosp.
  • Nakamura Takashi
    Lab. of Mol. Pharmacol., Biosignal Research Center, Kobe Univ. Dept. of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural Univ. of Med.
  • Sakaguchi Hirofumi
    Dept. of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural Univ. of Med.
  • Ninoyu Yuzuru
    Lab. of Mol. Pharmacol., Biosignal Research Center, Kobe Univ.
  • Saito Naoaki
    Lab. of Mol. Pharmacol., Biosignal Research Center, Kobe Univ.
  • Ueyama Takehiko
    Lab. of Mol. Pharmacol., Biosignal Research Center, Kobe Univ.

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Other Title
  • 蝸牛有毛細胞分化後におけるRac1とRac3の機能は有毛細胞にとり必須ではない

Abstract

<p>The Rho-family GTPases play various functions, including cytoskeletal regulation and cell polarity establishment. Using Cdc42-KO mice under the control of the Atoh1 promoter (Atoh1-Cre;Cdc42flox/flox), we previously reported that Cdc42 plays essential roles in the maintenance of cochlear hair cells (HCs) after HC specification. Although Rac1 and Rac3 have been reported to play important roles during embryonic development of the inner ear, little is known regarding their function in cochlear HCs after specification. Here, we revealed the localization and activation of Racs at stereocilia and apical junctional complexes in primary cochlear HCs using gene gun-mediated transfection of GFP-tagged Rac plasmids and transgenic mice expressing a Rac1- fluorescence resonance energy transfer (FRET) biosensor. To examine the roles of Racs after cochlear HC specification at individual levels, we generated conditional Rac-KO mice: Atoh1-Cre;Rac1flox/flox (Rac1-KO) and Atoh1-Cre;Rac1flox/flox;Rac3−/− (Rac1/Rac3-DKO) mice. Unexpectedly, both Rac1-KO and Rac1/Rac3-DKO mice exhibited normal cochlear HC morphology and normal hearing function. No hearing vulnerability was observed in young adult Rac1/Rac3-DKO mice even after intense noise exposure. Taken together, although Rac1 and Rac3 contribute to the early development of sensory epithelia in cochleae, they are dispensable after cochlear HC specification.</p>

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