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Originally published in Science Express on 13 January 2005
Science 18 February 2005:
Vol. 307. no. 5712, pp. 1114 - 1118
DOI: 10.1126/science.1106642
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Reports

Proliferation of Functional Hair Cells in Vivo in the Absence of the Retinoblastoma Protein

Cyrille Sage,1 Mingqian Huang,1 Kambiz Karimi,2 Gabriel Gutierrez,3 Melissa A. Vollrath,4 Duan-Sun Zhang,4 Jaime García-Añoveros,5 Philip W. Hinds,3 Jeffrey T. Corwin,2 David P. Corey,4 Zheng-Yi Chen1*

In mammals, hair cell loss causes irreversible hearing and balance impairment because hair cells are terminally differentiated and do not regenerate spontaneously. By profiling gene expression in developing mouse vestibular organs, we identified the retinoblastoma protein (pRb) as a candidate regulator of cell cycle exit in hair cells. Differentiated and functional mouse hair cells with a targeted deletion of Rb1 undergo mitosis, divide, and cycle, yet continue to become highly differentiated and functional. Moreover, acute loss of Rb1 in postnatal hair cells caused cell cycle reentry. Manipulation of the pRb pathway may ultimately lead to mammalian hair cell regeneration.

1 Neurology Service, MGH-HMS Center for Nervous System Repair, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
2 Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
3 Radiation Oncology, Molecular Oncology Research Institute, Tufts-New England Medical Center, Boston, MA 02111, USA.
4 Howard Hughes Medical Institute and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
5 Departments of Anesthesiology, Physiology, and Neurology, Northwestern University Institute for Neuroscience, Chicago, IL 60611, USA.

* To whom correspondence should be addressed. E-mail: zhengyi{at}helix.mgh.harvard.edu

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