Fukui A, Kishida S, Kikuchi A, Asashima M
Departmetn of Life Sciences (Biology), University of Tokyo, Japan.
Dev Growth Differ. 2000 Oct;42(5):489-98. doi: 10.1046/j.1440-169x.2000.00536.x.
Wnt signaling plays an important role in axis formation in early vertebrate development. Axin is one Wnt signaling regulator that inhibits this pathway. The effects of the injection of mRNA of several rat Axin (rAxin) mutants on axis formation in Xenopus embryos were examined. It was found that rAxin mutants containing only a regulation of G-protein signaling (RGS) domain fragment or with deletion of the RGS domain induced axis formation. Because the RGS domain is a major adenomatous polyposis coli gene product (APC)-binding domain, APC association with glycogen synthase kinase 3beta (GSK3beta) on the Axin molecule may be important in inhibition of axis formation. The ventralizing activities of wild-type rAxin and a mutant in which the Dishevelled and Axin (DIX) domain was deleted (deltaDIX mutant) were examined. Histological examination and gene expression revealed that the ventralizing activity of the deltaDIX mutant was weaker than that of wild-type rAxin. This finding suggests that the C-terminus of rAxin contributes to the inhibition of Wnt signaling in Xenopus embryos. Furthermore, an rAxin mutant that contained both the RGS and GSK3beta-binding domains affected both the dorsal and ventral sides of blastomeres, mediated ectodermal fate and induced expansion of notochord and/or endoderm, but did not induce axis formation.
Wnt信号通路在脊椎动物早期发育的轴形成过程中发挥着重要作用。Axin是一种抑制该信号通路的Wnt信号调节因子。研究了几种大鼠Axin(rAxin)突变体的mRNA注射对非洲爪蟾胚胎轴形成的影响。发现仅含有G蛋白信号调节(RGS)结构域片段或缺失RGS结构域的rAxin突变体可诱导轴形成。由于RGS结构域是腺瘤性息肉病大肠杆菌基因产物(APC)的主要结合结构域,APC与Axin分子上的糖原合酶激酶3β(GSK3β)的结合在抑制轴形成中可能很重要。检测了野生型rAxin和缺失Dishevelled与Axin(DIX)结构域的突变体(δDIX突变体)的腹化活性。组织学检查和基因表达显示,δDIX突变体的腹化活性弱于野生型rAxin。这一发现表明,rAxin的C末端有助于抑制非洲爪蟾胚胎中的Wnt信号通路。此外,同时包含RGS和GSK3β结合结构域的rAxin突变体影响了卵裂球的背侧和腹侧,介导了外胚层命运并诱导了脊索和/或内胚层的扩张,但未诱导轴形成。