Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning
Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning
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DOI：
10.1038/ng1178
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发表时间：
2003-07-01
期刊：
影响因子：
30.8
通讯作者：
Harland, RM
中科院分区：
文献类型：
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作者：
Khokha, MK;Hsu, D;Harland, RM
在肢体生长过程中，骨形态发生蛋白（BMP）的信号传导必须被调节，以维持极化活性区（ZPA）和顶端外胚层嵴（AER）之间的信号传导回路。Gremlin是一种细胞外BMP拮抗剂，已被提出来实现这一功能，因此在肢体造型中很重要。我们通过突变编码gremlin（Cktsf1b1，本文称为gremlin）的小鼠基因直接测试了这个模型。在突变的肢体中，ZPA和AER之间的反馈回路中断，导致异常的骨骼模式。我们还表明，gremlin突变是等位基因的肢体畸形突变（ld）。虽然BMP及其拮抗剂在肢体发育中具有多种作用，但这些实验表明gremlin是早期肢体生长和形成模式所需的主要BMP拮抗剂。
During limb outgrowth, signaling by bone morphogenetic proteins (BMPs) must be moderated to maintain the signaling loop between the zone of polarizing activity (ZPA) and the apical ectodermal ridge (AER). Gremlin, an extracellular BMP antagonist, has been proposed to fulfill this function and therefore be important in limb patterning. We tested this model directly by mutating the mouse gene encoding gremlin (Cktsf1b1, herein called gremlin). In the mutant limb, the feedback loop between the ZPA and the AER is interrupted, resulting in abnormal skeletal pattern. We also show that the gremlin mutation is allelic to the limb deformity mutation (ld). Although BMPs and their antagonists have multiple roles in limb development, these experiments show that gremlin is the principal BMP antagonist required for early limb outgrowth and patterning.