文章基本信息

标题：Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar papilla and mammalian cochlea
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作者：Eun Jin Son ; Ji-Hyun Ma ; Harinarayana Ankamreddy 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：12
页码：3746-3751
DOI：10.1073/pnas.1417856112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceSound frequency discrimination is crucial for daily activities throughout the animal kingdom. This process begins at the auditory peripheral organ known as the organ of Corti in mammals and basilar papilla in birds. This frequency tuning is facilitated by specific anatomical and physiological properties, including gradual changes in the shape of the mechanosensory hair cells and the total number of stereocilia per hair cell along the cochlea. Unlike in birds, the molecular mechanism(s) that establishes this tonotopic organization is not known in mammals. In this study, we provide in vivo evidence that Sonic Hedgehog signaling mediates regional identity of the developing cochlea in both mammals and birds, and this regional identity prefigures the tonotopic organization in the basilar papilla. Sound frequency discrimination begins at the organ of Corti in mammals and the basilar papilla in birds. Both of these hearing organs are tonotopically organized such that sensory hair cells at the basal (proximal) end respond to high frequency sound, whereas their counterparts at the apex (distal) respond to low frequencies. Sonic hedgehog (Shh) secreted by the developing notochord and floor plate is required for cochlear formation in both species. In mice, the apical region of the developing cochlea, closer to the ventral midline source of Shh, requires higher levels of Shh signaling than the basal cochlea farther away from the midline. Here, gain-of-function experiments using Shh-soaked beads in ovo or a mouse model expressing constitutively activated Smoothened (transducer of Shh signaling) show up-regulation of apical genes in the basal cochlea, even though these regionally expressed genes are not necessarily conserved between the two species. In chicken, these altered gene expression patterns precede morphological and physiological changes in sensory hair cells that are typically associated with tonotopy such as the total number of stereocilia per hair cell and gene expression of an inward rectifier potassium channel, IRK1, which is a bona fide feature of apical hair cells in the basilar papilla. Furthermore, our results suggest that this conserved role of Shh in establishing cochlear tonotopy is initiated early in development by Shh emanating from the notochord and floor plate.
关键词：frequency discrimination ; regional identity ; Inhba ; A2m ; Efnb2