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Novel genes involved in canonical Wnt/beta-catenin signaling pathway in early Ciona intestinalis embryos

机译:新的基因参与早期Ciona肠胚的规范Wnt /β-catenin信号通路

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We report here characterization of five genes for novel components of the canonical Wnt/beta-catenin signaling pathway. These genes were identified in the ascidian Ciona intestinalis through a loss-of-function screening for genes required for embryogenesis with morpholinos, and four of them have counterparts in vertebrates. The five genes we studied are as follows: Ci-PGAP1, a Ciona orthologue of human PGAP1, which encodes GPI (glycosylphosphatidylinositol) inositol-deacylase, Ci-ZF278, a gene encoding a C2H2 zinc-finger protein, Ci-C10orf11, a Ciona orthologue of human C10orf11 that encodes a protein with leucine-rich repeats, Ci-Spatial/C4orf17, a single counterpart for two human genes Spatial and C4orf17, and Ci-FLJ10634, a Ciona orthologue of human FLJ10634 that encodes a member of the J-protein family. Knockdown of each of the genes mimicked beta-catenin knockdown and resulted in suppression of the expression of beta-catenin downstream genes (Ci-FoxD, Ci-Lhx3, Ci-Otx and Ci-Fgf9/16/20) and subsequent endoderm formation. For every gene, defects in knockdown embryos were rescued by overexpression of a constitutively active form, but not wild-type, of Ci-beta-catenin. Dosage-sensitive interactions were found between Ci-beta-catenin and each of the genes. These results suggest that these five genes act upstream of or parallel to Ci-beta-catenin in the Wnt/beta-catenin signaling pathway in early Ciona embryos.
机译:我们在这里报告的经典Wnt /β-catenin信号通路的新型组件的五个基因的表征。通过功能损失筛选吗啉代胚胎发生所需的基因,在海生小肠Ciona肠中鉴定了这些基因,其中四个在脊椎动物中具有对应基因。我们研究的五个基因如下:Ci-PGAP1,人PGAP1的Ciona直向同源物,编码GPI(糖基磷脂酰肌醇)肌醇脱酰基酶,Ci-ZF278,编码C2H2锌指蛋白的基因,Ci-C10orf11,Ciona编码具有富亮氨酸重复序列的蛋白质的人C10orf11直向同源物,两个人基因Spatial和C4orf17的单个对应物Ci-Spatial / C4orf17和人FLJ10634的Ciona直向同源物Ci-FLJ10634,其编码J-蛋白质家族。每个基因的敲除模仿了β-catenin的敲除,并导致β-catenin下游基因(Ci-FoxD,Ci-Lhx3,Ci-Otx和Ci-Fgf9 / 16/20)的表达受到抑制,并随后形成了内胚层。对于每个基因,通过过表达Ci-beta-catenin的组成型活性形式而非野生型,可以挽救敲除胚胎中的缺陷。在Ci-β-catenin和每个基因之间发现了剂量敏感性相互作用。这些结果表明,这五个基因在早期Ciona胚胎Wnt /β-catenin信号传导途径中的Ci-β-catenin上游或与之平行。

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