ArticleCell cycle (Georgetown, Tex.)2011
Overlapping and distinct pRb pathways in the mammalian auditory and vestibular organs.
Article in Cell cycle (Georgetown, Tex.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Greater epithelial ridge cells are the principal organoid-forming progenitors of the mouse cochlea.Cell reports · 2021Article
- Spatiotemporally controlled overexpression of cyclin D1 triggers generation of supernumerary cells in the postnatal mouse inner ear.Hearing research · 2020Article
- Characterization of the transcriptomes ofAmerican journal of stem cells · 2020Article
- Renewed proliferation in adult mouse cochlea and regeneration of hair cells.Nature communications · 2019Article
- Gene expression profiling of the inner ear.Journal of anatomy · 2016Review
- Comprehensive Expression of Wnt Signaling Pathway Genes during Development and Maturation of the Mouse Cochlea.PloS one · 2016Article
- Article
- Quantitative High-Resolution Cellular Map of the Organ of Corti.Cell reports · 2015Article
- Gene Expression by Mouse Inner Ear Hair Cells during Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Auditory hair cell-specific deletion of p27Kip1 in postnatal mice promotes cell-autonomous generation of new hair cells and normal hearing.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- A historical to present-day account of efforts to answer the question: "what puts the brakes on mammalian hair cell regeneration?".Hearing research · 2013Review
- Postnatal development, maturation and aging in the mouse cochlea and their effects on hair cell regeneration.Hearing research · 2013Review
- Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein.Biochemical and biophysical research communications · 2013Article
- Regulation of p27Kip1 by Sox2 maintains quiescence of inner pillar cells in the murine auditory sensory epithelium.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Understanding the evolution and development of neurosensory transcription factors of the ear to enhance therapeutic translation.Cell and tissue research · 2012Review
- In vivo proliferative regeneration of balance hair cells in newborn mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Filling the silent void: genetic therapies for hearing impairment.Genetics research international · 2012Article
- MYC gene delivery to adult mouse utricles stimulates proliferation of postmitotic supporting cells in vitro.PloS one · 2012Article
- p27(Kip1) is required to maintain proliferative quiescence in the adult cochlea and pituitary.Cell cycle (Georgetown, Tex.) · 2011Article
- Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression.PloS one · 2011Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 4 countries.
Funding
Abstract
Retinoblastoma gene (Rb1) is required for proper cell cycle exit in the developing mouse inner ear and its deletion in the embryo leads to proliferation of sensory progenitor cells that differentiate into hair cells and supporting cells. In a conditional hair cell Rb1 knockout mouse, Pou4f3-Cre-pRb(-/-), pRb(-/-) utricular hair cells differentiate and survive into adulthood whereas differentiation and survival of pRb(-/-) cochlear hair cells are impaired. To comprehensively survey the pRb pathway in the mammalian inner ear, we performed microarray analysis of (pRb(-/-) cochlea and utricle. The comparative analysis shows that the core pathway shared between pRb(-/-) cochlea and utricle is centered on E2F, the key pathway that mediates pRb function. A majority of differentially expressed genes and enriched pathways are not shared but uniquely associated with pRb(-/-) cochlea or utricle. In pRb(-/-) cochlea, pathways involved in early inner ear development such as Wnt/β-catenin and Notch were enriched, whereas pathways involving in proliferation and survival are enriched in pRb(-/-) utricle. Clustering analysis showed that the pRb(-/-) inner ear has characteristics of a younger control inner ear, an indication of delayed differentiation. We created a transgenic mouse model (ER-Cre-pRb(flox/flox)) in which Rb1 can be acutely deleted postnatally. Acute Rb1 deletion in the adult mouse fails to induce proliferation or cell death in inner ear, strongly indicating that Rb1 loss in these postmitotic tissues can be effectively compensated for, or that pRb-mediated changes in the postmitotic compartment result in events that are functionally irreversible once enacted. This study thus supports the concept that pRb-regulated pathways relevant to hair cell development, encompassing proliferation, differentiation and survival, act predominantly during early development.
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