Essential role of POU–domain factor Brn-3c in auditory and vestibular hair cell development
- Mengqing Xiang*,†,
- Lin Gan†,‡,
- Daqing Li†,§,
- Zhi-Yong Chen*,
- Lijuan Zhou¶,‖,
- Bert W. O’Malley, Jr.§,
- William Klein‡,**, and
- Jeremy Nathans¶,‖,**,‡‡
- *Center for Advanced Biotechnology and Medicine, Department of Pediatrics, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, Piscataway, NJ 08854; ‡Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; Departments of §Otolaryngology, Head and Neck Surgery, ¶Molecular Biology and Genetics, ‡‡Neuroscience and Ophthalmology, ‖Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205
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Contributed by Jeremy Nathans
Abstract
The Brn-3 subfamily of POU–domain transcription factor genes consists of three highly homologous members—Brn-3a, Brn-3b, and Brn-3c—that are expressed in sensory neurons and in a small number of brainstem nuclei. This paper describes the role of Brn-3c in auditory and vestibular system development. In the inner ear, the Brn-3c protein is found only in auditory and vestibular hair cells, and the Brn-3a and Brn-3b proteins are found only in subsets of spiral and vestibular ganglion neurons. Mice carrying a targeted deletion of the Brn-3c gene are deaf and have impaired balance. These defects reflect a complete loss of auditory and vestibular hair cells during the late embryonic and early postnatal period and a secondary loss of spiral and vestibular ganglion neurons. Together with earlier work demonstrating a loss of trigeminal ganglion neurons and retinal ganglion cells in mice carrying targeted disruptions in the Brn-3a and Brn-3b genes, respectively, the Brn-3c phenotype reported here demonstrates that each of the Brn-3 genes plays distinctive roles in the somatosensory, visual, and auditory/vestibular systems.
Footnotes
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↵ † M.X., L.G., and D.L. contributed equally to this work and should be considered co-first authors.
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↵ ** To whom reprint requests should be addressed.
- ABBREVIATIONS:
- ES,
- embryonic stem;
- E,
- embryonic day;
- SPL,
- sound pressure level;
- DAPI,
- 4′,6-diamidino-2-phenylindole;
- P,
- postembryonic day
- Copyright © 1997, The National Academy of Sciences of the USA
