Brain-Specific Angiogenesis Inhibitor 3 Is Expressed in the Cochlea and Is Necessary for Hearing Function in Mice

Author:

Saegusa Chika12,Kakegawa Wataru3ORCID,Miura Eriko3,Aimi Takahiro3,Mogi Sachiyo4,Harada Tatsuhiko5,Yamashita Taku4,Yuzaki Michisuke3ORCID,Fujioka Masato126ORCID

Affiliation:

1. Department of Molecular Genetics, Kitasato University School of Medicine, Kanagawa 252-0374, Japan

2. Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan

3. Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan

4. Department of Otorhinolaryngology, Head and Neck Surgery, Kitasato University, Kanagawa 252-0374, Japan

5. Department of Otolaryngology, International University of Health and Welfare, Shizuoka 413-0012, Japan

6. Clinical and Translational Research Center, Keio University Hospital, Tokyo 162-8582, Japan

Abstract

Mammalian auditory hair cells transduce sound-evoked traveling waves in the cochlea into nerve stimuli, which are essential for hearing function. Pillar cells located between the inner and outer hair cells are involved in the formation of the tunnel of Corti, which incorporates outer-hair-cell-driven fluid oscillation and basilar membrane movement, leading to the fine-tuned frequency-specific perception of sounds by the inner hair cells. However, the detailed molecular mechanism underlying the development and maintenance of pillar cells remains to be elucidated. In this study, we examined the expression and function of brain-specific angiogenesis inhibitor 3 (Bai3), an adhesion G-protein-coupled receptor, in the cochlea. We found that Bai3 was expressed in hair cells in neonatal mice and pillar cells in adult mice, and, interestingly, Bai3 knockout mice revealed the abnormal formation of pillar cells, with the elevation of the hearing threshold in a frequency-dependent manner. Furthermore, old Bai3 knockout mice showed the degeneration of hair cells and spiral ganglion neurons in the basal turn. The results suggest that Bai3 plays a crucial role in the development and/or maintenance of pillar cells, which, in turn, are necessary for normal hearing function. Our results may contribute to understanding the mechanisms of hearing loss in human patients.

Funder

Grants-in-Aid for Specially Promoted Research

Grants-in-Aid for Challenging Research

Japan Society for the Promotion of Science, Takeda Science Foundation, and Taiju Life Social Welfare Foundation

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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