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Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears

Nature Neuroscience volume 3, pages 580–586 (2000)Cite this article

Abstract

For mammalian cochlear hair cells, fate determination is normally completed by birth. We report here that overexpression of Math1, a mouse homolog of the Drosophila gene atonal, in postnatal rat cochlear explant cultures resulted in extra hair cells. Surprisingly, we found that the source of the ectopic hair cells was columnar epithelial cells located outside the sensory epithelium in the greater epithelial ridge, which normally give rise to inner sulcus cells. Moreover, Math1 expression also facilitated conversion of postnatal utricular supporting cells into hair cells. Thus Math1 was sufficient for the production of hair cells in the ear, and immature postnatal mammalian inner ears retained the competence to generate new hair cells.

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Figure 1: Overexpression of Math1 leads to robust production of extra hair cells in the GER of P0 rat cochlear explant cultures.
Figure 2: Morphological and immunocytochemical conversion of the GER cells into hair cells.
Figure 3: Ultrastructural analysis of ectopically induced hair cells.
Figure 4: Math1 induces a gradual morphological change in the GER cells.
Figure 5: Quantitative analysis of the gradual induction of hair cell differentiation at various culture times.
Figure 6: Math1 facilitates conversion of utricular supporting cells into hair cells.

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Acknowledgements

We thank R. Kageyama for providing the Math1 cDNA (pCMV-Math1 plasmid) and M. Murone for providing the pRK5-EGFP plasmid for reconstruction of the pRK5-Math1-EGFP plasmid. We also thank T. Hasson for the anti-myosin VIIa antibody, M. Xiang for the pRK5SK-mBrn3c plasmid, A. Rosenthal and H. Sobkowicz for discussions, J. Shou for reading the manuscript, L. Rangell and G. Keller for electron microscopy, H. Aaron for confocal microscopy and A. Bruce for preparing the figures.

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  1. Department of Neuroscience, MS #72, Genentech, Inc., 1 DNA Way, South San Francisco, 94080, California, USA

    J. Lisa Zheng & Wei-Qiang Gao

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  1. J. Lisa Zheng
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Correspondence to Wei-Qiang Gao.

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Zheng, J., Gao, WQ. Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears. Nat Neurosci 3, 580–586 (2000). https://doi.org/10.1038/75753

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