The transcription factor Pou4f3 is essential for the survival of postnatal and adult mouse cochlear hair cells and normal hearing
IntroductionHair cells (HCs) of the cochlea are responsible for sound transduction and hearing perception in mammals. Genetic mutations in the transcription factor Pou4f3 cause non-syndromic autosomal dominant hearing loss in humans (DFNA15) which varies in the age of onset depending on the individu...
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2024.1369282/full |
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| author | Jarnail Singh Michelle R. Randle Bradley J. Walters Brandon C. Cox Brandon C. Cox |
| author_facet | Jarnail Singh Michelle R. Randle Bradley J. Walters Brandon C. Cox Brandon C. Cox |
| author_sort | Jarnail Singh |
| collection | DOAJ |
| description | IntroductionHair cells (HCs) of the cochlea are responsible for sound transduction and hearing perception in mammals. Genetic mutations in the transcription factor Pou4f3 cause non-syndromic autosomal dominant hearing loss in humans (DFNA15) which varies in the age of onset depending on the individual mutation. Mouse models with germline deletion or mutations in Pou4f3 have previously demonstrated its critical role in the maturation and survival of cochlear HCs during embryonic development. However, the role of Pou4f3 in auditory function and in the survival or maintenance of cochlear HCs after birth and during adulthood has not been studied.MethodsTherefore, using the inducible CreER-loxP system, we deleted Pou4f3 from mouse cochlear HCs at different postnatal ages, relevant to specific stages of HC maturation and hearing function.Results and discussionElevated auditory brainstem response thresholds and significant HC loss were detected in mice with Pou4f3 deletion compared to their control littermates, regardless of the age when Pou4f3 was deleted. However, HC loss occurred more rapidly when Pou4f3 was deleted from immature HCs. Additionally, HC loss caused by Pou4f3 deletion did not affect the number of cochlear supporting cells, but caused a delayed loss of spiral ganglion neurons at 4 months after the deletion. In conclusion, Pou4f3 is necessary for the survival of cochlear HCs and normal hearing at all postnatal ages regardless of their maturation state. Our data also suggest that Pou4f3 indirectly regulates the survival of spiral ganglion neurons. |
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| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-24T22:40:19Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-43fff87f4bf14a459715f8c063c4f1c62024-03-19T04:27:37ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022024-03-011810.3389/fncel.2024.13692821369282The transcription factor Pou4f3 is essential for the survival of postnatal and adult mouse cochlear hair cells and normal hearingJarnail Singh0Michelle R. Randle1Bradley J. Walters2Brandon C. Cox3Brandon C. Cox4Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, United StatesDepartment of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, United StatesDepartment of Otolaryngology-Head and Neck Surgery, University of Mississippi Medical Center, Jackson, MS, United StatesDepartment of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, United StatesDepartment of Otolaryngology, Southern Illinois University School of Medicine, Springfield, IL, United StatesIntroductionHair cells (HCs) of the cochlea are responsible for sound transduction and hearing perception in mammals. Genetic mutations in the transcription factor Pou4f3 cause non-syndromic autosomal dominant hearing loss in humans (DFNA15) which varies in the age of onset depending on the individual mutation. Mouse models with germline deletion or mutations in Pou4f3 have previously demonstrated its critical role in the maturation and survival of cochlear HCs during embryonic development. However, the role of Pou4f3 in auditory function and in the survival or maintenance of cochlear HCs after birth and during adulthood has not been studied.MethodsTherefore, using the inducible CreER-loxP system, we deleted Pou4f3 from mouse cochlear HCs at different postnatal ages, relevant to specific stages of HC maturation and hearing function.Results and discussionElevated auditory brainstem response thresholds and significant HC loss were detected in mice with Pou4f3 deletion compared to their control littermates, regardless of the age when Pou4f3 was deleted. However, HC loss occurred more rapidly when Pou4f3 was deleted from immature HCs. Additionally, HC loss caused by Pou4f3 deletion did not affect the number of cochlear supporting cells, but caused a delayed loss of spiral ganglion neurons at 4 months after the deletion. In conclusion, Pou4f3 is necessary for the survival of cochlear HCs and normal hearing at all postnatal ages regardless of their maturation state. Our data also suggest that Pou4f3 indirectly regulates the survival of spiral ganglion neurons.https://www.frontiersin.org/articles/10.3389/fncel.2024.1369282/fullPou4f3DFNA15hearing losshair cell maturationhair cell survival |
| spellingShingle | Jarnail Singh Michelle R. Randle Bradley J. Walters Brandon C. Cox Brandon C. Cox The transcription factor Pou4f3 is essential for the survival of postnatal and adult mouse cochlear hair cells and normal hearing Frontiers in Cellular Neuroscience Pou4f3 DFNA15 hearing loss hair cell maturation hair cell survival |
| title | The transcription factor Pou4f3 is essential for the survival of postnatal and adult mouse cochlear hair cells and normal hearing |
| title_full | The transcription factor Pou4f3 is essential for the survival of postnatal and adult mouse cochlear hair cells and normal hearing |
| title_fullStr | The transcription factor Pou4f3 is essential for the survival of postnatal and adult mouse cochlear hair cells and normal hearing |
| title_full_unstemmed | The transcription factor Pou4f3 is essential for the survival of postnatal and adult mouse cochlear hair cells and normal hearing |
| title_short | The transcription factor Pou4f3 is essential for the survival of postnatal and adult mouse cochlear hair cells and normal hearing |
| title_sort | transcription factor pou4f3 is essential for the survival of postnatal and adult mouse cochlear hair cells and normal hearing |
| topic | Pou4f3 DFNA15 hearing loss hair cell maturation hair cell survival |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2024.1369282/full |
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