Journal article
Atoh1 directs hair cell differentiation and survival in the late embryonic mouse inner ear
Developmental biology, Vol.381(2), pp.401-410
09/15/2013
DOI: 10.1016/j.ydbio.2013.06.022
PMCID: PMC3772529
PMID: 23796904
Abstract
Atoh1 function is required for the earliest stages of inner ear hair cell development, which begins during the second week of gestation. Atoh1 expression in developing hair cells continues until early postnatal ages, but the function of this late expression is unknown. To test the role of continued Atoh1 expression in hair cell maturation we conditionally deleted the gene in the inner ear at various embryonic and postnatal ages. In the organ of Corti, deletion of Atoh1 at E15.5 led to the death of all hair cells. In contrast, deletion at E16.5 caused death only in apical regions, but abnormalities of stereocilia formation were present throughout the cochlea. In the utricle, deletion at E14.5 or E16.5 did not cause cell death but led to decreased expression of myosin VIIa and failure of stereocilia formation. Furthermore, we show that maintained expression of Barhl1 and Gfi1, two transcription factors implicated in cochlear hair cell survival, depends upon continued Atoh1 expression. However, maintained expression of Pou4f3 and several hair cell-specific markers is independent of Atoh1 expression. These data reveal novel late roles for Atoh1 that are separable from its initial role in hair cell development.
•Late Atoh1 expression regulates cochlear hair cell survival and then differentiation.•In the utricle, late Atoh1 expression regulates differentiation but not survival.•Atoh1 maintains expression of Barhl1 and Gfi1 but not Pou4f3 or other hair cell markers.
Details
- Title: Subtitle
- Atoh1 directs hair cell differentiation and survival in the late embryonic mouse inner ear
- Creators
- Kurt T Chonko - Department of Developmental Biology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15090, USAIsrat Jahan - Department of Biology, University of Iowa, Iowa City, IA 52242, USAJennifer Stone - Department of Otolaryngology/Head and Neck Surgery, Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, WA 98195, USAMargaret C Wright - Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106, USATomoyuki Fujiyama - Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187-8502, JapanMikio Hoshino - Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187-8502, JapanBernd Fritzsch - Department of Biology, University of Iowa, Iowa City, IA 52242, USAStephen M Maricich - Richard King Mellon Foundation Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15090, USA
- Resource Type
- Journal article
- Publication Details
- Developmental biology, Vol.381(2), pp.401-410
- DOI
- 10.1016/j.ydbio.2013.06.022
- PMID
- 23796904
- PMCID
- PMC3772529
- NLM abbreviation
- Dev Biol
- ISSN
- 0012-1606
- eISSN
- 1095-564X
- Publisher
- Elsevier Inc
- Grant note
- name: Child Neurology Society (SMM); DOI: 10.13039/100002583, name: American Hearing Research Foundation (SMM); DOI: 10.13039/100002046, name: Health Hearing Foundation (IJ); DOI: 10.13039/100000055, name: NIDCD, award: R01 DC003696; name: NIDCD P30 Core, award: DC004661; name: NIH, award: T32 GM008056; DOI: 10.13039/100000055, name: NIDCD, award: R01 DC005590; name: P30 Core, award: DC010362
- Language
- English
- Date published
- 09/15/2013
- Academic Unit
- Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984070316702771
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