Int. J. Dev. Biol. 51: 585 - 595 (2007)
doi: 10.1387/ijdb.072387sr
© UPV/EHU Press

Pocket proteins and cell cycle regulation in inner ear development

Sonia M.S. Rocha-Sanchez1,2,* and Kirk W. Beisel2

1Creighton University School of Dentistry, Dept of Oral Biology and 2School of Medicine, Dept. of Biomedical Sciences Omaha, NE, USA

ABSTRACT Loss of neurosensory cells of the ear, caused by genetic and non-genetic factors, is becoming an increasing problem as people age, resulting in deafness and vestibular disorders. Unveiling useful mechanisms of cell cycle regulation may offer the possibility to generate new cells out of remaining ones, thus providing the cellular basis to induce new hair cell differentiation in the mammalian ear. Here, we provide an overview of cell cycle regulating genes in general and of those studied in the ear in particular. We categorize those genes into regulators that act upstream of the pocket proteins and into those that act downstream of the pocket proteins. The three members of the pocket protein family essentially determine, through interaction with the eight members of the E2F family, whether or not the cell cycle will progress to the S-phase and thus cell division. The abundant presence of one or more members of these families in adult hair cells supports the notion that inhibition of cell cycle progression through these proteins is a lifelong process. Indeed, manipulating some of those proteins, unfortunately, leads to abortive entry into the cell cycle. Combined with recent success to induce hair cell differentiation through molecular therapy, these approaches may provide a viable strategy to restore lost hair cells in the inner ear.


hair cell regeneration, transdifferentiation, cell cycle, E2F transcription factor, pocket protein

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