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抑制NF-kappaB活动导致顶端外皮脊的破坏和异常的四肢形态发生
P B Bushdid1, D M Brantley, F E Yull
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2363, USA.
Nature
|April 29, 1998
概括
核因子-卡帕B (NF-kappaB) 对于肢体芽的发育至关重要,形成顶端外皮脊 (AER). 抑制NF-kappaB会破坏四肢的形成,导致发育缺陷和基因表达的改变.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 背部蛋白质塑造了Drosophila的胚胎背部腹部轴.
- 背脊的脊椎动物同类是核因子-卡帕B (NF-kappaB).
研究的目的:
- 研究NF-kappaB在脊椎动物四肢芽发育中的作用.
- 了解NF-kappaB是如何调节角外皮脊 (AER) 形成和四肢形态发生的.
主要方法:
- 病毒介导的NF-kappaB抑制剂在成长中的肢体芽中的输送.
- 分析AER形态,四肢大小和远端元素发育的分析.
- 对关键发育基因 (Sonic hedgehog,Twist,BMP-4) 的基因表达分析,以应对NF-kappaB抑制.
主要成果:
- NF-kappaB对于AER形成和适当的四肢组织至关重要.
- 干扰NF-kappaB活动导致异形AER,肢体大小减少和远端元素的损失.
- 抑制NF-kappaB会改变Sonic hedgehog,Twist和骨形态遗传蛋白-4在四肢介质中的表达.
结论:
- 脊椎动物NF-kappaB蛋白对于胚胎肢体形成过程中,外皮和介质体之间传输生长因子信号至关重要.
- 在肢体芽形态发生过程中,NF-kappaB在调节其原瘤基因c-rel的转录中发挥着关键作用.
- 这些发现确立了NF-kappaB在通过ectoderm-mesenchyme信号传递协调肢体发育中的新功能.
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