Defects in hair cells disrupt the development of auditory peripheral circuitry
Abstract Deafness is the most common form of sensory impairment in humans and frequently caused by defects in hair cells of the inner ear. Here we demonstrate that in male mice which model recessive non-syndromic deafness (DFNB6), inactivation of Tmie in hair cells disrupts gene expression in the ne...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55275-x |
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| author | Riley T. Bottom Yijun Xu Caroline Siebald Jinsei Jung Ulrich Müller |
| author_facet | Riley T. Bottom Yijun Xu Caroline Siebald Jinsei Jung Ulrich Müller |
| author_sort | Riley T. Bottom |
| collection | DOAJ |
| description | Abstract Deafness is the most common form of sensory impairment in humans and frequently caused by defects in hair cells of the inner ear. Here we demonstrate that in male mice which model recessive non-syndromic deafness (DFNB6), inactivation of Tmie in hair cells disrupts gene expression in the neurons that innervate them. This includes genes regulating axonal pathfinding and synaptogenesis, two processes that are disrupted in the inner ear of the mutant mice. Similar defects are observed in mouse models for deafness caused by mutations in other genes with primary functions in hair cells. Gene therapy targeting hair cells restores hearing and inner ear circuitry in DFNB6 model mice. We conclude that hair cell function is crucial for the establishment of peripheral auditory circuitry. Treatment modalities for deafness thus need to consider restoration of the function of both hair cells and neurons, even when the primary defect occurs in hair cells. |
| format | Article |
| id | doaj-art-b241e3ba3ddd439caedae8f51bb0d63f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b241e3ba3ddd439caedae8f51bb0d63f2025-01-05T12:36:18ZengNature PortfolioNature Communications2041-17232024-12-0115112010.1038/s41467-024-55275-xDefects in hair cells disrupt the development of auditory peripheral circuitryRiley T. Bottom0Yijun Xu1Caroline Siebald2Jinsei Jung3Ulrich Müller4The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of MedicineThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of MedicineThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of MedicineDepartment of Otorhinolaryngology, Yonsei University College of MedicineThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of MedicineAbstract Deafness is the most common form of sensory impairment in humans and frequently caused by defects in hair cells of the inner ear. Here we demonstrate that in male mice which model recessive non-syndromic deafness (DFNB6), inactivation of Tmie in hair cells disrupts gene expression in the neurons that innervate them. This includes genes regulating axonal pathfinding and synaptogenesis, two processes that are disrupted in the inner ear of the mutant mice. Similar defects are observed in mouse models for deafness caused by mutations in other genes with primary functions in hair cells. Gene therapy targeting hair cells restores hearing and inner ear circuitry in DFNB6 model mice. We conclude that hair cell function is crucial for the establishment of peripheral auditory circuitry. Treatment modalities for deafness thus need to consider restoration of the function of both hair cells and neurons, even when the primary defect occurs in hair cells.https://doi.org/10.1038/s41467-024-55275-x |
| spellingShingle | Riley T. Bottom Yijun Xu Caroline Siebald Jinsei Jung Ulrich Müller Defects in hair cells disrupt the development of auditory peripheral circuitry Nature Communications |
| title | Defects in hair cells disrupt the development of auditory peripheral circuitry |
| title_full | Defects in hair cells disrupt the development of auditory peripheral circuitry |
| title_fullStr | Defects in hair cells disrupt the development of auditory peripheral circuitry |
| title_full_unstemmed | Defects in hair cells disrupt the development of auditory peripheral circuitry |
| title_short | Defects in hair cells disrupt the development of auditory peripheral circuitry |
| title_sort | defects in hair cells disrupt the development of auditory peripheral circuitry |
| url | https://doi.org/10.1038/s41467-024-55275-x |
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