Nucleoredoxin regulates the Wnt/planar cell polarity pathway in Xenopus
Nucleoredoxin regulates the Wnt/planar cell polarity pathway in Xenopus
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DOI：
10.1111/j.1365-2443.2008.01220.x
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发表时间：
2008-09-01
期刊：
影响因子：
2.1
通讯作者：
Miki, Hiroaki
中科院分区：
文献类型：
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作者：
Funato, Yosuke;Michiue, Tatsuo;Miki, Hiroaki
Wnt信号通路在物种间是保守的，对早期发育至关重要。我们之前发现核氧还蛋白（NRX）是一种在体内与dishevelxed （Dvl）相互作用以负向调节Wnt/ β -catenin通路的蛋白质。然而，NRX是否影响Wnt通路的另一个分支，即Wnt/平面细胞极性（PCP）通路尚不清楚。我们发现NRX调节Wnt/PCP通路。在非洲爪蟾中，分别通过注射NRX mRNA或反义morpholino寡核苷酸来过度表达或消耗NRX，会产生弯曲轴表型，这种表型通常在PCP通路活性异常的胚胎中观察到。在Dvl和NRX mRNA共注射实验中，NRX抑制Dvl诱导的弯曲轴表型。NRX的过度表达或缺失也会抑制被认为是正常原肠胚形成基础的会聚伸展运动。我们还发现NRX可以抑制dvl诱导的c-Jun磷酸化上调。这些结果表明NRX通过Dvl参与Wnt/PCP通路，调控爪蟾原肠形成运动。
The Wnt signaling pathway is conserved across species, and is essential for early development. We previously identified nucleoredoxin (NRX) as a protein that interacts with dishevelled (Dvl) in vivo to negatively regulate the Wnt/beta-catenin pathway. However, whether NRX affects another branch of the Wnt pathway, the Wnt/planar cell polarity (PCP) pathway, remains unclear. Here we show that NRX regulates the Wnt/PCP pathway. In Xenopus laevis, over-expression or depletion of NRX by injection of NRX mRNA or antisense morpholino oligonucleotide, respectively, yields the bent-axis phenotype that is typically observed in embryos with abnormal PCP pathway activity. In co-injection experiments of Dvl and NRX mRNA, NRX suppresses the Dvl-induced bent-axis phenotype. Over-expression or depletion of NRX also suppresses the convergent extension movements that are believed to underlie normal gastrulation. We also found that NRX can inhibit Dvl-induced up-regulation of c-Jun phosphorylation. These results indicate that NRX plays crucial roles in the Wnt/PCP pathway through Dvl and regulates Xenopus gastrulation movements.