한빛사논문
- 조회895
Hei Yeun Koo 1,2, Min-A Kim 3, Hyehyun Min 1, Jae Yeon Hwang 4, Meenakshi Prajapati-DiNubila 5, Kwan Soo Kim 1,2, Martin M Matzuk 6,7, Juw Won Park 4, Angelika Doetzlhofer 5, Un-Kyung Kim 3, Jinwoong Bok 1,2,8
1Department of Anatomy, Yonsei University College of Medicine, Seoul 03722, Korea.
2Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.
3Department of Biology, Kyungpook National University, Daegu 41566, Korea.
4Department of Computer Science and Engineering, University of Louisville, Louisville, KY 40292.
5Department of Neuroscience, The Solomon H. Snyder, Johns Hopkins University, School of Medicine, Baltimore, MD 21205.
6Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030.
7Center for Drug Discovery, Baylor College of Medicine, Houston, TX 77030.
8Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 03722, Korea.
To whom correspondence may be addressed. : Jinwoong Bok
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.
논문정보
- Research article
- 2023년 01월 (BRIC 등록일 2023-01-27)
- 국내(교신)+국외 연구진
- 생명과학 > 발생생물학
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