环素D1在视网膜和乳腺中提供了发育和瘤发生之间的联系
P Sicinski1, J L Donaher, S B Parker
1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
Cell
|August 25, 1995
概括
缺乏细胞循环的关键调节剂环素D1的小鼠表现出发育问题,包括神经障碍和减少活力. 这突显了环素D1在细胞增殖中的关键作用,特别是在视网膜和乳腺中.
科学领域:
- 发育生物学是发展生物学.
- 细胞周期调节细胞周期调节
- 分子遗传学 分子遗传学
背景情况:
- 环素D1是细胞周期的关键调节剂,控制通过G1阶段的进展.
- 它在组织发育和特定器官系统中的精确作用需要进一步阐明.
- 基因向提供了一个强大的工具来研究特定基因的体内功能.
研究的目的:
- 在小鼠中研究循环素D1缺乏的生理和发育后果.
- 确定cyclin D1在特定组织的增殖中的作用,包括视网膜和乳腺.
- 为了探索在乳腺发育中的cyclin D1和类固醇激素信号传递之间的关系.
主要方法:
- 在胚胎干细胞中准基因以产生缺乏环素D1的小鼠.
- 对缺乏cyclin D1的动物进行表型分析,包括对身体大小,活力和神经功能的评估.
- 视网膜的组织学检查,以评估细胞数量和增殖能力.
- 在现场杂交以确定正常小鼠胚胎中的cyclin D1表达模式.
- 在怀孕期间对成年突变女性乳腺发育的分析.
主要成果:
- 缺乏环素D1的小鼠是可活的,但体型减小,活力下降和神经系统缺陷.
- 由于胚胎增殖受损,视网膜细胞数量显著减少,与正常视网膜中的高环林D1表达相关.
- 成年突变雌性在怀孕期间表现出乳腺上皮质增殖失败,尽管卵巢类固醇激素水平正常.
- 这些发现表明,cyclin D1在调解类固醇诱导的乳腺增殖方面发挥了关键作用.
结论:
- 环素D1对于正常的胚胎发育至关重要,特别是对视网膜中的细胞增殖至关重要.
- 视网膜表现出对循环素D1的特殊依赖,以使其正常发育.
- 在怀孕期间,Cyclin D1作为类固醇激素诱导乳腺上皮质增殖的关键调解剂.
- 向cyclin D1可能为涉及异常细胞增殖的疾病提供治疗策略.
相关概念视频
01:45Positive Regulator Molecules
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02:39Positive Regulator Molecules
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02:34Inhibition of Cdk Activity
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M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
02:34Inhibition of CDK Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...