ArticleProceedings of the National Academy of Sciences of the United States of America2015
Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar papilla and mammalian cochlea.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 55 citations in OpenAlex.
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- TMEM145 is a key stereociliary component in the link structures of outer hair cells and mediates the secretion of stereocilin and tubby.Nature communications · 2025Article
- Multifaceted roles of sonic hedgehog signaling in mammalian inner ear development.Developmental biology · 2025Review
- Biallelic variants of SEMA3F are associated with nonsyndromic hearing loss.Molecules and cells · 2025Article
- Mitochondrial dynamics regulate cell morphology in the developing cochlea.Development (Cambridge, England) · 2024Article
- 3D reconstruction of the mouse cochlea from scRNA-seq data suggests morphogen-based principles in apex-to-base specification.Developmental cell · 2024Article
- Mapping the developmental potential of mouse inner ear organoids at single-cell resolution.iScience · 2024Article
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- Variants of LRP2, encoding a multifunctional cell-surface endocytic receptor, associated with hearing loss and retinal dystrophy.Clinical genetics · 2023Article
- Early radial positional information in the cochlea is optimized by a precise linear BMP gradient and enhanced by SOX2.Scientific reports · 2023Article
- Regeneration of Hair Cells from Endogenous Otic Progenitors in the Adult Mammalian Cochlea: Understanding Its Origins and Future Directions.International journal of molecular sciences · 2023Review
- Follistatin regulates the specification of the apical cochlea responsible for low-frequency hearing in mammals.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Alternative splicing in shaping the molecular landscape of the cochlea.Frontiers in cell and developmental biology · 2023Review
- Article
- TiAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- In vitro and in vivo models: What have we learnt about inner ear regeneration and treatment for hearing loss?Molecular and cellular neurosciences · 2022Review
- Molecular Pathways Modulating Sensory Hair Cell Regeneration in Adult Mammalian Cochleae: Progress and Perspectives.International journal of molecular sciences · 2021Review
- Mapping the regulatory landscape of auditory hair cells from single-cell multi-omics data.Genome research · 2021Article
- Assessing evidence for adaptive evolution in two hearing-related genes important for high-frequency hearing in echolocating mammals.G3 (Bethesda, Md.) · 2021Article
- Position Specific Alternative Splicing and Gene Expression Profiles Along the Tonotopic Axis of Chick Cochlea.Frontiers in molecular biosciences · 2021Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
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Abstract
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.
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