Dysregulation of sonic hedgehog signaling causes hearing loss in ciliopathy mouse models

Kyeong-Hye Moon; Ji-Hyun Ma; Hyehyun Min; Heiyeun Koo; HongKyung Kim; Hyuk Wan Ko; Jinwoong Bok

doi:10.7554/elife.56551

journal article Open Access Dec 31, 2020

Dysregulation of sonic hedgehog signaling causes hearing loss in ciliopathy mouse models

Kyeong-Hye Moon

Ji-Hyun Ma Hyehyun Min Heiyeun Koo HongKyung Kim Hyuk Wan Ko Jinwoong Bok

eLife Vol. 9 · eLife Sciences Publications, Ltd

View at Publisher Save 10.7554/elife.56551

Abstract

Defective primary cilia cause a range of diseases known as ciliopathies, including hearing loss. The etiology of hearing loss in ciliopathies, however, remains unclear. We analyzed cochleae from three ciliopathy mouse models exhibiting different ciliogenesis defects:
Intraflagellar transport 88
(
Ift88
),
Tbc1d32
(a.k.a.
bromi
), and
Cilk1
(a.k.a.
Ick
) mutants. These mutants showed multiple developmental defects including shortened cochlear duct and abnormal apical patterning of the organ of Corti. Although ciliogenic defects in cochlear hair cells such as misalignment of the kinocilium are often associated with the planar cell polarity pathway, our results showed that inner ear defects in these mutants are primarily due to loss of sonic hedgehog signaling. Furthermore, an inner ear-specific deletion of
Cilk1
elicits low-frequency hearing loss attributable to cellular changes in apical cochlear identity that is dedicated to low-frequency sound detection. This type of hearing loss may account for hearing deficits in some patients with ciliopathies.

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Published: Dec 31, 2020
Vol/Issue: 9
License: View

Authors

K

Kyeong-Hye Moon

Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea; BK21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea

J

Ji-Hyun Ma

Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea

H

Hyehyun Min

Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea

H

Heiyeun Koo

Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea; BK21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea

H

HongKyung Kim

Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea

H

Hyuk Wan Ko

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea

J

Jinwoong Bok

Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea; BK21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea

Funding

National Research Foundation of Korea Award: NRF-2014M3A9D5A01073865

Cite This Article

Kyeong-Hye Moon, Ji-Hyun Ma, Hyehyun Min, et al. (2020). Dysregulation of sonic hedgehog signaling causes hearing loss in ciliopathy mouse models. eLife, 9. https://doi.org/10.7554/elife.56551

Dysregulation of sonic hedgehog signaling causes hearing loss in ciliopathy mouse models

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