遗传证据表明,FGFs在四肢近端-远端模式中起着指导作用
Francesca V Mariani1, Christina P Ahn, Gail R Martin
1Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California at San Francisco, San Francisco, California 94158-2324, USA.
Nature
|May 2, 2008
概括
来自角外皮脊的纤维细胞生长因子 (FGF) 对四肢发育至关重要. 这项研究表明,FGF8是足够的,但FGF的组合指导四肢模式,挑战以前的模型.
科学领域:
- 发育生物学 发展生物学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 顶端外皮脊 (AER) 在近端-远端 (P-D) 轴上为四肢发育提供信号.
- 纤维细胞生长因子 (FGFs) 是关键的AER衍生信号,在小鼠AER中表达Fgf4,Fgf8,Fgf9和Fgf17.
研究的目的:
- 研究特定的AER-FGFs在小鼠四肢发育和模式形成中的作用.
- 为了确定AER-FGF信号是指导性的还是允许性的.
主要方法:
- 产生和分析缺乏AER-FGF基因组合的复合突变小鼠系 (Fgf4,Fgf8,Fgf9,Fgf17).
- 检查突变四肢芽的骨模式和基因表达.
主要成果:
- 缺少Fgf4,Fgf9和Fgf17的老鼠肢体显示正常的骨模式,表明Fgf8充足.
- 仅仅Fgf8的失活会导致轻微的缺陷,但与其他AER-FGF基因移除相结合,会导致越来越严重的骨表型.
- AER-FGFs调节P-D模式的基因表达和细胞存活,在指定远端四肢领域中起到指导作用.
结论:
- AER-FGF在指定远端四肢领域方面发挥了指导作用,挑战了长期以来的允许信号假设.
- 多个AER-FGF的联合贡献对正常的四肢发育和模式形成至关重要.
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