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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 : e56551, 2020-12 
Journal Title
Issue Date
Animals ; Cell Polarity / physiology* ; Cilia / metabolism ; Ciliopathies / physiopathology* ; Disease Models, Animal ; Embryo, Mammalian / metabolism ; Gene Expression Regulation, Developmental / genetics* ; Hair Cells, Auditory / metabolism ; Hearing Loss / physiopathology* ; Hedgehog Proteins / metabolism* ; Mice ; Wnt Signaling Pathway / physiology
ciliopathies ; developmental biology ; hearing loss ; mouse ; primary cilia ; sonic hedgehog
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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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Advanced Medical Science Research and Education (첨단의과학교육연구단) > Journal Papers
Yonsei Authors
Ma, Ji Hyun(마지현) ORCID logo https://orcid.org/0000-0002-7215-9040
Moon, Kyeong-Hye(문경혜)
Min, Hye Hyun(민혜현) ORCID logo https://orcid.org/0000-0001-5450-5088
Bok, Jin Woong(복진웅) ORCID logo https://orcid.org/0000-0003-1958-1872
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