1. Developmental Biology
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Dysregulation of sonic hedgehog signaling causes hearing loss in ciliopathy mouse models

  1. Kyeong-Hye Moon
  2. Ji-Hyun Ma
  3. Hyehyun Min
  4. Heiyeun Koo
  5. HongKyung Kim
  6. Hyuk Wan Ko  Is a corresponding author
  7. Jinwoong Bok  Is a corresponding author
  1. Yonsei University, Republic of Korea
Research Article
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Cite this article as: eLife 2020;9:e56551 doi: 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.

Article and author information

Author details

  1. Kyeong-Hye Moon

    Anatomy, Yonsei University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  2. Ji-Hyun Ma

    Anatomy, Yonsei University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  3. Hyehyun Min

    Anatomy, Yonsei University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  4. Heiyeun Koo

    Anatomy, Yonsei University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  5. HongKyung Kim

    Anatomy, Yonsei University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  6. Hyuk Wan Ko

    Biochemistry, Yonsei University, Seoul, Republic of Korea
    For correspondence
    KOHW@YONSEI.AC.KR
    Competing interests
    The authors declare that no competing interests exist.
  7. Jinwoong Bok

    Anatomy, Yonsei University, Seoul, Republic of Korea
    For correspondence
    bokj@yuhs.ac
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1958-1872

Funding

National Research Foundation of Korea (NRF-2014M3A9D5A01073865)

  • Jinwoong Bok

National Research Foundation of Korea (NRF-2016R1A5A2008630)

  • Jinwoong Bok

National Research Foundation of Korea (NRF-2017R1A2B3009133)

  • Jinwoong Bok

National Research Foundation of Korea (NRF-2014M3A9D5A01073969)

  • Hyuk Wan Ko

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal protocols were approved by the Institutional Animal Care and Use Committee (IACUC) at Yonsei University College of Medicine with NIH guidelines (No. 2018-0023).

Reviewing Editor

  1. Jeremy F Reiter, University of California, San Francisco, United States

Publication history

  1. Received: March 2, 2020
  2. Accepted: December 31, 2020
  3. Accepted Manuscript published: December 31, 2020 (version 1)
  4. Version of Record published: January 13, 2021 (version 2)

Copyright

© 2020, Moon et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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