Developmental regulation of oscillatory expression

振荡表达的发育调节

基本信息

  • 批准号:
    9146394
  • 负责人:
  • 金额:
    $ 31.57万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-09-18 至 2019-05-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): The vertebrate segmentation clock is a model biological oscillator that generates periodic pattern in developing embryos. The segmentation clock controls somitogenesis, the process by which the mesoderm of the vertebrate animal is sequentially divided into segmental units called somites. At the core of the segmentation clock is an auto-inhibitory negative feedback loop involving her/Hes transcriptional repressors. Although the `clock and wave front' model of somitogenesis is widely accepted, there are still many aspects of clock regulation that are not understood, and yet other aspects that may be challenged as our ability to examine oscillation dynamics in vivo becomes more sophisticated. It is only over the last few years that we have been able to watch the segmentation clock oscillate in living embryos and only very recently that have we been able to do so with single cell resolution. As our ability to detect rapid biological oscillations improves, more and more examples of biological oscillators controlling diverse cellular responses and cell fate decisions are being discovered, underscoring a critical need to understand how they are regulated. In this proposal, we will focus on characterizing the cis regulatory elements and trans-acting factors required for a largely understudied but critical aspect of oscillatory systems - that of cyclic transcript decay. Rapid transcript turnover is critical in oscillatory systems like the vertebrate segmentation clock, where every round of transcription must be followed by a wave of transcript decay to sustain oscillations. We already have one factor in hand, Pnrc2, which will greatly facilitate the identification of a cyclic transcript "decay complex". We anticipate that this work ill broadly impact our understanding of regulation of RNA turnover in many developmental contexts. Rapid molecular oscillators are not only important for generating segmental pattern during development, but also for promoting heterogeneous responses in neural stem cells, and for biasing embryonic stem cells toward different cell fates. Additionally, Hes1 upregulation promotes rhabdomyosarcoma, an aggressive childhood cancer. Thus, the more we understand cyclic regulation, the more likely we are to develop promising treatments or therapeutics for human disease. We propose to uncover regulatory mechanisms, elements, and factors that control oscillation dynamics in one such oscillatory system, the vertebrate segmentation clock, and anticipate that our work will impact studies in fields as diverse as developmental biology, stem cell biology, tissue engineering, and possibly cancer cell biology.


项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Sharon L Amacher其他文献

Sharon L Amacher的其他文献

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{{ truncateString('Sharon L Amacher', 18)}}的其他基金

Survival Motor Neuron (SMN) function in motoneuron development
运动神经元存活 (SMN) 在运动神经元发育中的功能
  • 批准号:
    9899326
  • 财政年份:
    2017
  • 资助金额:
    $ 31.57万
  • 项目类别:
Developmental regulation of oscillatory expression
振荡表达的发育调节
  • 批准号:
    10299003
  • 财政年份:
    2015
  • 资助金额:
    $ 31.57万
  • 项目类别:
Developmental regulation of oscillatory expression
振荡表达的发育调节
  • 批准号:
    9055984
  • 财政年份:
    2015
  • 资助金额:
    $ 31.57万
  • 项目类别:
Developmental regulation of oscillatory expression
振荡表达的发育调节
  • 批准号:
    10631091
  • 财政年份:
    2015
  • 资助金额:
    $ 31.57万
  • 项目类别:
Developmental regulation of oscillatory expression
振荡表达的发育调节
  • 批准号:
    10456210
  • 财政年份:
    2015
  • 资助金额:
    $ 31.57万
  • 项目类别:
Developmental regulation of oscillatory expression
振荡表达的发育调节
  • 批准号:
    9322167
  • 财政年份:
    2015
  • 资助金额:
    $ 31.57万
  • 项目类别:
Developmental regulation of oscillatory expression
振荡表达的发育调节
  • 批准号:
    10799064
  • 财政年份:
    2015
  • 资助金额:
    $ 31.57万
  • 项目类别:
Strategic Conference of Zebrafish Investigators
斑马鱼研究人员战略会议
  • 批准号:
    10012784
  • 财政年份:
    2013
  • 资助金额:
    $ 31.57万
  • 项目类别:
Strategic Conference of Zebrafish Investigators
斑马鱼研究人员战略会议
  • 批准号:
    10470396
  • 财政年份:
    2013
  • 资助金额:
    $ 31.57万
  • 项目类别:
Strategic Conference of Zebrafish Investigators
斑马鱼研究人员战略会议
  • 批准号:
    8604722
  • 财政年份:
    2013
  • 资助金额:
    $ 31.57万
  • 项目类别:

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