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

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


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 low36 quency 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.

Original languageEnglish
Article numbere56551
Pages (from-to)1-63
Number of pages63
Publication statusPublished - 2020 Dec

Bibliographical note

Funding Information:
We thank Dr. Doris Wu for critical reading of the manuscript, Dr. Ping Chen and Dr. Sun Myoung Kim for providing Ift88 cKO embryo samples for initial study, and members of the Bok laboratory for constructive discussion of the manuscript. This work was supported by grants from the National Research Foundation of Korea (NRF-2014M3A9D5A01073865, NRF-2016R1A5A2008630, and NRF-2017R1A2B3009133 to J.B.; NRF-2014M3A9D5A01073969 to H.W.K.).

Publisher Copyright:
© 2020, eLife Sciences Publications Ltd. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)


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