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

• Published in: eLife Vol. 9
• Main Authors: Moon, Kyeong-Hye, Ma, Ji-Hyun, Min, Hyehyun, Koo, Heiyeun, Kim, HongKyung, Ko, Hyuk Wan, Bok, Jinwoong
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 31.12.2020; eLife Sciences Publications, Ltd; eLife Sciences Publications Ltd
• Subjects: Analysis; Animals; Cell Polarity - physiology; Cilia - metabolism; ciliopathies; Ciliopathies - physiopathology; Developmental Biology; Disease Models, Animal; Embryo, Mammalian - metabolism; Gene Expression Regulation, Developmental - genetics; Hair Cells, Auditory - metabolism; Hearing loss; Hearing Loss - physiopathology; Hedgehog Proteins - metabolism; Mice; primary cilia; sonic hedgehog; Wnt Signaling Pathway - physiology; sonic hedgehog; mouse; hearing loss; ciliopathies; developmental biology; primary cilia
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.56551

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: ( ), (a.k.a. ), and (a.k.a. ) 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 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.