Proliferation of functional hair cells in vivo in the absence of the retinoblastoma protein.
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.
Sage
Cyrille
C
Neurology Service, MGH-HMS Center for Nervous System Repair, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Huang
Mingqian
M
Karimi
Kambiz
K
Gutierrez
Gabriel
G
Vollrath
Melissa A
MA
Zhang
Duan-Sun
DS
García-Añoveros
Jaime
J
Hinds
Philip W
PW
Corwin
Jeffrey T
JT
Corey
David P
DP
Chen
Zheng-Yi
ZY
D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D003051:Cochlea / Q000166:cytology / Q000196:embryology; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D016161:Genes, Retinoblastoma; D006199:Hair Cells, Auditory, Inner / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D012038:Regeneration; D016160:Retinoblastoma Protein / Q000235:genetics / Q000502:physiology*; D012444:Saccule and Utricle / Q000196:embryology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
C073804:FM1 43; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D016160:Retinoblastoma Protein