Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Johnson & Johnson

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

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
Prev | Table of Contents | Next

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

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Rapid cell-cycle reentry and cell death after acute inactivation of the retinoblastoma gene product in postnatal cochlear hair cells.
T. Weber, M. K. Corbett, L. M. L. Chow, M. B. Valentine, S. J. Baker, and J. Zuo (2008)
PNAS 105, 781-785
   Abstract »    Full Text »    PDF »
Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine.
C. L. Stoick-Cooper, R. T. Moon, and G. Weidinger (2007)
Genes & Dev. 21, 1292-1315
   Abstract »    Full Text »    PDF »
Shape Change Controls Supporting Cell Proliferation in Lesioned Mammalian Balance Epithelium.
J. R. Meyers and J. T. Corwin (2007)
J. Neurosci. 27, 4313-4325
   Abstract »    Full Text »    PDF »
p19Ink4d and p21Cip1 Collaborate to Maintain the Postmitotic State of Auditory Hair Cells, Their Codeletion Leading to DNA Damage and p53-Mediated Apoptosis.
H. Laine, A. Doetzlhofer, J. Mantela, J. Ylikoski, M. Laiho, M. F. Roussel, N. Segil, and U. Pirvola (2007)
J. Neurosci. 27, 1434-1444
   Abstract »    Full Text »    PDF »
Essential role of retinoblastoma protein in mammalian hair cell development and hearing.
C. Sage, M. Huang, M. A. Vollrath, M. C. Brown, P. W. Hinds, D. P. Corey, D. E. Vetter, and Z.-Y. Chen (2006)
PNAS 103, 7345-7350
   Abstract »    Full Text »    PDF »
Regeneration of vestibular otolith afferents after ototoxic damage..
M. Zakir and J. D. Dickman (2006)
J. Neurosci. 26, 2881-2893
   Abstract »    Full Text »    PDF »
Appendage Regeneration in Adult Vertebrates and Implications for Regenerative Medicine.
J. P. Brockes and A. Kumar (2005)
Science 310, 1919-1923
   Abstract »    Full Text »    PDF »
The Notch ligands DLL1 and JAG2 act synergistically to regulate hair cell development in the mammalian inner ear.
A. E. Kiernan, R. Cordes, R. Kopan, A. Gossler, and T. Gridley (2005)
Development 132, 4353-4362
   Abstract »    Full Text »    PDF »
The retinoblastoma gene pathway regulates the postmitotic state of hair cells of the mouse inner ear.
J. Mantela, Z. Jiang, J. Ylikoski, B. Fritzsch, E. Zacksenhaus, and U. Pirvola (2005)
Development 132, 2377-2388
   Abstract »    Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)