一个Fgf/Gremlin抑制反循环触发了肢体芽外生长的终止
1Laboratory of Genetics, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Nature
|July 3, 2008
概括
一个新的自我终止电路调节器官大小. 纤维细胞生长因子 (FGF) 信号抑制Gremlin1 (Grem1),创建一个抑制循环,平衡四肢芽生长和终止.
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:
- 器官形成和再生需要精确控制促进生长和限制信号,以达到刻板印象的尺寸.
- 肢体芽的生长受到一个积极的反循环的调节,涉及纤维细胞生长因子 (FGF),声波刺 (Shh) 和格林林1 (Grem1).
研究的目的:
- 调查肢体大小终止背后的机制,特别是老鼠肢体中信号终止的序列.
- 确定除了目前接受的肢体生长控制模型之外的替代监管机制.
主要方法:
- 分析FGF/Shh/Grem1正反循环中缺少基因的复合小鼠突变.
- 基因分析以确定信号通路之间的新型调节相互作用.
主要成果:
- 证明FGF信号可以抑制Gremlin1 (Grem1) 表达,建立了一个新的FGF/Grem1抑制循环.
- 这种抑制依赖于高的FGF活性,并且发生在老鼠和的四肢中.
- 这些发现揭示了自我促进 (积极的FGF/Shh循环) 和自我终止 (FGF/Grem1抑制循环) 电路调节外生长.
结论:
- 一个新的FGF/Grem1抑制循环与积极的FGF/Shh循环协同作用,以控制四肢的大小.
- 这种自我调节电路确保以与不同物种观察到的模式相一致的方式终止生长信号.
- 识别的电路为了解组织大小调节在多种发育和再生环境中的理解提供了一个框架.
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