The mouse fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation

The mouse fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation
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DOI:
10.1016/s0092-8674(00)80324-4
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发表时间:
1997-07-11
期刊:
影响因子:
64.5
通讯作者:
Costantini, F
Costantini, F
中科院分区:
生物学1区
文献类型:
--
作者:
Zeng, L;Fagotto, F;Costantini, F

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小鼠融合基因的突变具有多效性发育效应,包括在纯合子胚胎中形成轴向复制。融合基因的产物Axin与RGS(G蛋白信号调节因子)和蓬乱的蛋白质相似。导致轴向复制的突变融合等位基因扰乱了主要的mRNA,表明Axin负向调节对轴诱导信号的反应。将Axin mRNA注射到非洲爪哇胚胎中,通过干扰Wnt途径的信号来抑制背轴的形成。此外,腹侧注射缺乏RGS结构域的Axin mRNA可诱导异位轴,显然是通过显性-负性机制。因此,Axin是Wnt信号的一种新的抑制剂,并调节哺乳动物和两栖动物胚轴形成的早期步骤。
Mutations at the mouse Fused locus have pleiotropic developmental effects, including the formation of axial duplications in homozygous embryos. The product of the Fused locus, Axin, displays similarities to RGS (Regulators of G-Protein Signaling) and Dishevelled proteins. Mutant Fused alleles that cause axial duplications disrupt the major mRNA, suggesting that Axin negatively regulates the response to an axis-inducing signal. Injection of Axin mRNA into Xenopus embryos inhibits dorsal axis formation by interfering with signaling through the Wnt pathway. Furthermore, ventral injection of an Axin mRNA lacking the RGS domain induces an ectopic axis, apparently through a dominant-negative mechanism. Thus, Axin is a novel inhibitor of Wnt signaling and regulates an early step in embryonic axis formation in mammals and amphibians.