Developmental differentiation of mouse inner ear neuron subpopulations resolved with a peripherin-promoter reporter within the Grm8 locus
Abstract Molecular profiling of inner ear neurons has broadened the classification of the primary afferents that support neural coding for hearing and balance. To extend spatiotemporal characterization of auditory and vestibular neuron diversity, we established a transgenic reporter mouse model (Prp...
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Nature Portfolio
2025-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-94011-3 |
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| author | Lily J. Pearson Jeremy L. Pinyon Jennie M. E. Cederholm Georg von Jonquieres Florence Bartlett Xabier Vázquez-Campos Fabien Delerue Lars M. Ittner Gary D. Housley |
| author_facet | Lily J. Pearson Jeremy L. Pinyon Jennie M. E. Cederholm Georg von Jonquieres Florence Bartlett Xabier Vázquez-Campos Fabien Delerue Lars M. Ittner Gary D. Housley |
| author_sort | Lily J. Pearson |
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| description | Abstract Molecular profiling of inner ear neurons has broadened the classification of the primary afferents that support neural coding for hearing and balance. To extend spatiotemporal characterization of auditory and vestibular neuron diversity, we established a transgenic reporter mouse model (Prph p-mCherry), where elements of the peripherin promoter (Prph p) drive expression of the mCherry fluorescent reporter. Type III intermediate filament protein peripherin expression is a marker for type II spiral ganglion neurons (SGN) that innervate the cochlear outer hair cells, and the small diameter ‘bouton’ vestibular ganglion neurons (VGN) innervating the type II vestibular hair cells. Using Nanopore genome sequencing, the integration site of the transgene construct was identified within the class III metabotropic glutamate receptor 8 gene (Grm8, chromosome 6). Use of CUBIC / PEGASOS clearing of early postnatal to adult inner ear tissues enabled in situ 3D spatial localization of a dispersed population of cochlear mCherry + ve SGN, with highest expression and density in the hook (high frequency encoding) basal region. Of these mCherry + ve SGN, type II SGN (peripherin-immunopositive) were all co-labeled in the basal region, but the majority of the overall mCherry-delineated SGN auditory subpopulation were type I SGN innervating inner hair cells. In the VGN, mCherry + ve neurons represented ~ 15% of the adult population, dispersed as a small diameter subpopulation throughout both the inferior and superior VGN regions. These findings resolve heterogeneous type I and type II cochlear SGN subpopulations, particularly in the structurally complex hook region, and further differentiate vestibular primary afferents across postnatal development. |
| format | Article |
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| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-3d84ca12b1ec47008715dc9b43cb570e2025-08-20T02:10:12ZengNature PortfolioScientific Reports2045-23222025-03-0115112010.1038/s41598-025-94011-3Developmental differentiation of mouse inner ear neuron subpopulations resolved with a peripherin-promoter reporter within the Grm8 locusLily J. Pearson0Jeremy L. Pinyon1Jennie M. E. Cederholm2Georg von Jonquieres3Florence Bartlett4Xabier Vázquez-Campos5Fabien Delerue6Lars M. Ittner7Gary D. Housley8Translational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, UNSWTranslational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, UNSWTranslational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, UNSWTranslational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, UNSWKGLMF Mark Wainwright Analytical Centre, UNSWSchool of Biotechnology and Biomolecular Sciences, UNSWDepartment of Genetics, The University of Texas MD Anderson Cancer CenterFaculty of Medicine, Health and Human Sciences, Department of Biomedical Sciences, Dementia Research Centre, Macquarie UniversityTranslational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, UNSWAbstract Molecular profiling of inner ear neurons has broadened the classification of the primary afferents that support neural coding for hearing and balance. To extend spatiotemporal characterization of auditory and vestibular neuron diversity, we established a transgenic reporter mouse model (Prph p-mCherry), where elements of the peripherin promoter (Prph p) drive expression of the mCherry fluorescent reporter. Type III intermediate filament protein peripherin expression is a marker for type II spiral ganglion neurons (SGN) that innervate the cochlear outer hair cells, and the small diameter ‘bouton’ vestibular ganglion neurons (VGN) innervating the type II vestibular hair cells. Using Nanopore genome sequencing, the integration site of the transgene construct was identified within the class III metabotropic glutamate receptor 8 gene (Grm8, chromosome 6). Use of CUBIC / PEGASOS clearing of early postnatal to adult inner ear tissues enabled in situ 3D spatial localization of a dispersed population of cochlear mCherry + ve SGN, with highest expression and density in the hook (high frequency encoding) basal region. Of these mCherry + ve SGN, type II SGN (peripherin-immunopositive) were all co-labeled in the basal region, but the majority of the overall mCherry-delineated SGN auditory subpopulation were type I SGN innervating inner hair cells. In the VGN, mCherry + ve neurons represented ~ 15% of the adult population, dispersed as a small diameter subpopulation throughout both the inferior and superior VGN regions. These findings resolve heterogeneous type I and type II cochlear SGN subpopulations, particularly in the structurally complex hook region, and further differentiate vestibular primary afferents across postnatal development.https://doi.org/10.1038/s41598-025-94011-3 |
| spellingShingle | Lily J. Pearson Jeremy L. Pinyon Jennie M. E. Cederholm Georg von Jonquieres Florence Bartlett Xabier Vázquez-Campos Fabien Delerue Lars M. Ittner Gary D. Housley Developmental differentiation of mouse inner ear neuron subpopulations resolved with a peripherin-promoter reporter within the Grm8 locus Scientific Reports |
| title | Developmental differentiation of mouse inner ear neuron subpopulations resolved with a peripherin-promoter reporter within the Grm8 locus |
| title_full | Developmental differentiation of mouse inner ear neuron subpopulations resolved with a peripherin-promoter reporter within the Grm8 locus |
| title_fullStr | Developmental differentiation of mouse inner ear neuron subpopulations resolved with a peripherin-promoter reporter within the Grm8 locus |
| title_full_unstemmed | Developmental differentiation of mouse inner ear neuron subpopulations resolved with a peripherin-promoter reporter within the Grm8 locus |
| title_short | Developmental differentiation of mouse inner ear neuron subpopulations resolved with a peripherin-promoter reporter within the Grm8 locus |
| title_sort | developmental differentiation of mouse inner ear neuron subpopulations resolved with a peripherin promoter reporter within the grm8 locus |
| url | https://doi.org/10.1038/s41598-025-94011-3 |
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