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Role of transcription factors a Brn-3.1 and Brn-3.2 in auditory and visual system development

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Abstract

THE neurally expressed genes Brn-3.1 and Brn-3.2 (refs 1–6) are mammalian orthologues of the Caenorhabditis elegans unc-86 gene7 that constitute, with Brn-3.0 (refs 1–3,8,9), the class IV POU-domain transcription factors10. Brn-3.1 and Brn-3.2 provide a means of exploring the potentially distinct biological functions of expanded gene families in neural development. The highly related members of the Brn-3 family have similar DNA-binding preferences1,2 and overlapping expression patterns in the sensory nervous system, midbrain and hindbrain1–6,8,9, suggesting functional redundancy. Here we report that Brn-3.1 and Brn-3.2 critically modulate the terminal differentiation of distinct sensorineural cells in which they exhibit selective spatial and temporal expression patterns. Deletion of the Brn-3.2 gene causes the loss of most retinal ganglion cells, defining distinct ganglion cell populations. Mutation of Brn-3.1 results in complete deafness, owing to a failure of hair cells to appear in the inner ear, with subsequent loss of cochlear and vestibular ganglia.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093, USA

    Linda Erkman, Robert J. McEvilly, Aimee K. Ryan, Farideh Hooshmand, Shawn M. O'Connell & Michael G. Rosenfeld

  2. Department of Surgery, Division of Anatomy, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093, USA

    David H. Rapaport

  3. VA Medical Center and Departments of Surgery/Otolaryngology and Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093, USA

    Lin Luo, Elizabeth M. Keithley & Alien F. Ryan

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  1. Linda Erkman
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  2. Robert J. McEvilly
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  3. Lin Luo
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  10. Michael G. Rosenfeld
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Erkman, L., McEvilly, R., Luo, L. et al. Role of transcription factors a Brn-3.1 and Brn-3.2 in auditory and visual system development. Nature 381, 603–606 (1996). https://doi.org/10.1038/381603a0

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  • DOI: https://doi.org/10.1038/381603a0

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