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

Author:

Lee Yun-Shain1,Liu Feng2,Segil Neil123

Affiliation:

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.

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.

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

Cited by 168 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3