Daple deficiency causes hearing loss in adult mice by inducing defects in cochlear stereocilia and apical microtubules

Yoshiyuki Ozono,Sachiko Tsukita,Kazuya Ohata,Yumi Ohta,Kazuo Oshima,Takao Imai,Hidenori Inohara,Takashi Sato,Shogo Nakayama,Maki Takagishi,Yukiko Hanada,Elisa Herawati,Atsushi Tamura,Masahide Takahashi

doi:10.1038/s41598-021-96232-8

Yoshiyuki Ozono, Sachiko Tsukita + Show 12 more

Open Access

https://doi.org/10.1038/s41598-021-96232-8

Copy DOI

Abstract

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. Recently, defects in hair bundle arrangement were reported in postnatal Dishevelled-associating protein (ccdc88c, alias Daple)-deficient mice. In the present study, we found that adult Daple−/− 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 adult 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, especially at high frequencies.

Highlights

The V-shaped arrangement of hair bundles on cochlear hair cells is critical for auditory sensing
We show the presence of hearing disturbances at all frequencies examined using the auditory brainstem response (ABR) test, especially at high frequencies
As localization and expression of Daple was similar between neonates and adults, along the apex to the base, in the cochlea (Fig. 1C,D; Supplementary Fig. S1), the hearing disturbances observed at all sound frequencies in Daple−/− mice are reasonable, disruption at higher frequencies suggested the presence of certain functional and/or structural failures involving hair cells (HCs) in the more basal regions of the OC

Summary

Introduction

The V-shaped arrangement of hair bundles on cochlear hair cells is critical for auditory sensing. Daple−/− mice, in the embryonic and neonatal stages, have previously been reported to have defects in the arrangement of hair bundles in cochlear HCs8, hearing-potential and morphological changes with age have not been analyzed.

Results

Conclusion