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First published online 21 June 2006
doi: 10.1242/dev.02453

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A morphogenetic wave of p27^Kip1 transcription directs cell cycle exit during organ of Corti development

Yun-Shain Lee^1,*, Feng Liu^2,* and Neil Segil^1,2,3,

¹ Gonda Department of Cell and Molecular Biology, House Ear Institute, 2100 West 3rd Street, Los Angeles, CA 90057, USA.
² Neuroscience Graduate Program, University of Southern California, Los Angeles, CA 90033, USA.
³ Department of Cell and Neurobiology, University of Southern California, Los Angeles, CA 90033, USA.

Author for correspondence (e-mail: nsegil{at}hei.org)

Accepted 9 May 2006

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 p27^Kip1 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 p27^Kip1 regulation have revealed important posttranscriptional mechanisms regulating p27^Kip1 abundance, little is known about how developmental patterns of p27^Kip1 expression, and thus cell cycle exit, are achieved. Here, we show that during inner ear development transcriptional regulation of p27^Kip1 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 p27^Kip1 gene occurs normally in p27^Kip1-null mice, indicating that developmental regulation of p27^Kip1 transcription is independent of the timing of cell cycle exit. In addition, cell-type-specific patterns of p27^Kip1 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 p27^Kip1 transcription and the control of cell number during sensory organ morphogenesis.

Key words: p27Kip1, Cell cycle, Development, Morphogenesis, Inner ear, Cochlea, Organ of Corti, Mouse

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