Silencing p27 reverses post-mitotic state of supporting cells in neonatal mouse cochleae

  title={Silencing p27 reverses post-mitotic state of supporting cells in neonatal mouse cochleae},
  author={Kazuya Ono and Takayuki Nakagawa and Ken Kojima and Masahiro Matsumoto and Takeshi Kawauchi and Mikio Hoshino and Juichi Ito},
  journal={Molecular and Cellular Neuroscience},

p27Kip1 is required to maintain proliferative quiescence in the adult cochlea and pituitary

Re-establishment of normal p27Kip1 expression in animals with established pituitary tumors, in an inducible “knock-on” model, led to cessation ofpituitary tumor growth, indicating the cells had maintained their susceptibility to p27-mediated growth suppression.

Restrictions in Cell Cycle Progression of Adult Vestibular Supporting Cells in Response to Ectopic Cyclin D1 Expression

Intensive barriers that limit proliferative capacity of utricular supporting cells are revealed that limit the ability of these cells to regenerate.

The Cyclin Dependent Kinase Inhibitor p27 Kip1 Maintains Terminal Differentiation in the Mouse Organ of Corti

It is reported that p27 deletion results in an increased number of inner and outer hair cells at one month of age and these hair cells display normal phenotypes including uptake of AM1-43, a mechanotransduction dye.

p27Kip1 Knockdown Induces Proliferation in the Organ of Corti in Culture after Efficient shRNA Lentiviral Transduction

The results revalidate the use of lentiviral vectors in the study and in the potential therapeutic approaches for inner ear diseases, as well as demonstrate that efficient manipulation of p27Kip1 is sufficient to induce significant proliferation in the postnatal cochlea.

Mature Mice Lacking Rbl2/p130 Gene Have Supernumerary Inner Ear Hair Cells and Supporting Cells

Unscheduled proliferation of SCs in the adult p130−/− cochlea coupled to downregulation of bona fide cell cycle inhibitors provides a mechanistic basis for the role of p130 as a regulator of SC and HC mitotic quiescence in the more apical regions of the cochrea.

MYC Gene Delivery to Adult Mouse Utricles Stimulates Proliferation of Postmitotic Supporting Cells In Vitro

The results indicate that ectopic expression of c-MycT58A in combination with methods for promoting cell survival and differentiation may restore regenerative potential to supporting cells within the adult mammalian inner ear.

Regulation of p27Kip1 by Sox2 Maintains Quiescence of Inner Pillar Cells in the Murine Auditory Sensory Epithelium

The studies suggest that manipulating Sox2 or p27Kip1 expression is an effective approach to inducing proliferation of neonatal auditory IPCs, an initial but necessary step toward restoring hearing in mammals.

Cell type-specific effects of p27KIP1 loss on retinal development

Although expressed in all retinal cell types, p27 is required to maintain the quiescence of specific cell types including bipolar cells, Müller glia, and cones while it is dispensable for preventing cell cycle reentry in other cell types.

LSD1 is Required for Hair Cell Regeneration in Zebrafish

The data suggest that downregulation of LSD1 significantly decreases hair cell regeneration after neomycin-induced hair cell loss through inactivation of the Wnt/β-catenin and Fgf signaling pathways, which might represent a novel biomarker and potential therapeutic approach for the treatment of hearing loss.



Gene disruption of p27(Kip1) allows cell proliferation in the postnatal and adult organ of corti.

It is reported that the cyclin-dependent kinase inhibitor p27(Kip1) is selectively expressed in the supporting-cell population of the organ of Corti, and may provide an important pathway for inducing hair-cell regeneration in the mammalian hearing organ.

Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells

It is shown that post-mitotic supporting cells purified from the postnatal mouse cochlea retain the ability to divide and trans-differentiate into new hair cells in culture, and that age-dependent changes in supporting cell proliferative capacity are due in part to changes in the able to downregulate the cyclin-dependent kinase inhibitor p27Kip1.

p27(Kip1) links cell proliferation to morphogenesis in the developing organ of Corti.

P27(Kip1) expression is induced in the primordial organ of Corti between E12 and E14, correlating with the cessation of cell division of the progenitors of the hair cells and supporting cells, providing a link between developmental control of cell proliferation and the morphological development of the inner ear.

Progressive hearing loss in mice lacking the cyclin-dependent kinase inhibitor Ink4d

It is reported that targeted deletion of Ink4d alone is sufficient to disrupt the maintenance of the post-mitotic state of sensory hair cells in post-natal mice, which identifies a novel mechanism underlying a non-syndromic form of progressive hearing loss in mice.

The retinoblastoma gene pathway regulates the postmitotic state of hair cells of the mouse inner ear

It is demonstrated that the pRb pathway is required for hair cell quiescence and that manipulation of the cell cycle machinery disrupts the coordinated development within the inner ear sensory epithelia.

p19Ink4d and p21Cip1 Collaborate to Maintain the Postmitotic State of Auditory Hair Cells, Their Codeletion Leading to DNA Damage and p53-Mediated Apoptosis

The demonstration of changing expression patterns of multiple CKIs in auditory hair cells during the stages of early postnatal maturation show that the maintenance of the postmitotic state is an active, tissue-specific process, cooperatively regulated by several CKIs, and is critical for the lifelong survival of these sensory cells.

Alteration in expression of p27 in auditory epithelia and neurons of mice during degeneration

Rapid cell-cycle reentry and cell death after acute inactivation of the retinoblastoma gene product in postnatal cochlear hair cells

It is concluded that Rb plays essential and age-dependent roles during HC proliferation and differentiation, and, in contrast to previous hypotheses, cell death after forced cell-cycle reentry presents a major challenge for mammalian HC regeneration from residual postnatal HCs.

Delta1 expression during avian hair cell regeneration.

Initial evidence is provided that Delta-Notch signaling may be involved in maintaining the correct cell types and patterns during postembryonic replacement of sensory epithelial cells in the chick inner ear.

Atoh1 expression defines activated progenitors and differentiating hair cells during avian hair cell regeneration

A role for Atoh1 is suggested in re‐specifying supporting cells and in biasing postmitotic cells toward the hair cell fate during hair cell regeneration in the mature chicken ear.