Cited by 187Hearing, Cochlea, Tinnitus, GeneticsDevelopmental Biology and Gene RegulationNeurogenesis and neuroplasticity mechanisms

A morphogenetic wave of p27Kip1 transcription directs cell cycle exit during organ of Corti development

Lee, Yun-Shain, Liu, Feng, Segil, Neil·2006·Development

Abstract

The molecular mechanisms coordinating cell cycle exit with cell differentiation and organogenesis are a crucial, yet poorly understood, aspect of normal development. The mammalian cyclin-dependent kinase inhibitor p27Kip1 is required for the correct timing of cell cycle exit in developing tissues, and thus plays a crucial role in this process. Although studies of p27Kip1 regulation have revealed important posttranscriptional mechanisms regulating p27Kip1 abundance, little is known about how developmental patterns of p27Kip1 expression,and thus cell cycle exit, are achieved. Here, we show that during inner ear development transcriptional regulation of p27Kip1 is the primary determinant of a wave of cell cycle exit that dictates the number of postmitotic progenitors destined to give rise to the hair cells and supporting cells of the organ of Corti. Interestingly, transcriptional induction from the p27Kip1 gene occurs normally in p27Kip1-null mice, indicating that developmental regulation of p27Kip1 transcription is independent of the timing of cell cycle exit. In addition, cell-type-specific patterns of p27Kip1 transcriptional regulation are observed in the mature organ of Corti and retina, suggesting that this mechanism is important in differential regulation of the postmitotic state. This report establishes a link between the spatial and temporal pattern of p27Kip1transcription and the control of cell number during sensory organ morphogenesis.

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Crossref · 10.1242/dev.02453

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Authors
Lee, Y.-S., Liu, F., & Segil, N.
Affiliations
  • House Clinic (US)
  • University of Southern California (US)
Venue
Development
Published
2006-08-01
Volume
133
Issue
15
Pages
2817-2826
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
OpenAlex
W2098102650
Cited by
187
References
81
Citations by year
2026: 3 · 2025: 8 · 2024: 2 · 2023: 8 · 2022: 7 · 2021: 13 · 2020: 12 · 2019: 12 · 2018: 8 · 2017: 9 · 2016: 9 · 2015: 10 · 2014: 9 · 2013: 12 · 2012: 9
FWCI
4.34
Type
journal article
Language
en
Open access
closed
Locations
  • Development (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Deafness and Other Communication Disorders (R01DC004189)
Topics
  • Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
p27, transcriptional regulation, cell cycle exit, hair cells, supporting cells, inner ear development, cyclin-dependent kinase inhibitors, retina
MeSH terms
Animals, Base Sequence, Cell Cycle, Mice, Transgenic, Organ of Corti, Transcription, Genetic, Polymerase Chain Reaction, DNA Primers, Mice, Knockout, Gene Expression Regulation, Developmental, Cyclin-Dependent Kinase Inhibitor p27, Mice

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