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Follistatin regulates the specification of the apical cochlea responsible for low-frequency hearing in mammals

Authors
 Hei Yeun Koo  ;  Min-A Kim  ;  Hyehyun Min  ;  Jae Yeon Hwang  ;  Meenakshi Prajapati-DiNubila  ;  Kwan Soo Kim  ;  Martin M Matzuk  ;  Juw Won Park  ;  Angelika Doetzlhofer  ;  Un-Kyung Kim  ;  Jinwoong Bok 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.120(1) : e2213099120, 2023-01 
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN
 0027-8424 
Issue Date
2023-01
MeSH
Animals ; Cochlea / physiology ; Follistatin* / genetics ; Hearing / physiology ; Hedgehog Proteins* / genetics ; Hedgehog Proteins* / metabolism ; Mammals / metabolism ; Mice
Keywords
cochlea ; follistatin ; frequency discrimination ; tonotopy
Abstract
The cochlea's ability to discriminate sound frequencies is facilitated by a special topography along its longitudinal axis known as tonotopy. Auditory hair cells located at the base of the cochlea respond to high-frequency sounds, whereas hair cells at the apex respond to lower frequencies. Gradual changes in morphological and physiological features along the length of the cochlea determine each region's frequency selectivity, but it remains unclear how tonotopy is established during cochlear development. Recently, sonic hedgehog (SHH) was proposed to initiate the establishment of tonotopy by conferring regional identity to the primordial cochlea. Here, using mouse genetics, we provide in vivo evidence that regional identity in the embryonic cochlea acts as a framework upon which tonotopy-specific properties essential for frequency selectivity in the mature cochlea develop. We found that follistatin (FST) is required for the maintenance of apical cochlear identity, but dispensable for its initial induction. In a fate-mapping analysis, we found that FST promotes expansion of apical cochlear cells, contributing to the formation of the apical cochlear domain. SHH, in contrast, is required both for the induction and maintenance of apical identity. In the absence of FST or SHH, mice produce a short cochlea lacking its apical domain. This results in the loss of apex-specific anatomical and molecular properties and low-frequency-specific hearing loss.
Full Text
https://www.pnas.org/doi/10.1073/pnas.2213099120
DOI
10.1073/pnas.2213099120
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
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
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/193764
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