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Requirement of Wnt/beta-catenin signaling in pronephric kidney development

机译:Wnt /β-catenin信号传导在肾前肾发育中的需求

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The pronephric kidney controls water and electrolyte balance during early fish and amphibian embryogenesis. Many Wnt signaling components have been implicated in kidney development. Specifically, in Xenopus pronephric development as well as the murine metanephroi, the secreted glycoprotein Wnt-4 has been shown to be essential for renal tubule formation. Despite the importance of Wnt signals in kidney organogenesis, little is known of the definitive downstream signaling pathway(s) that mediate their effects. Here we report that inhibition of Wnt/beta-catenin signaling within the pronephric field of Xenopus results in significant losses to kidney epithelial tubulogenesis with little or no effect on adjoining axis or somite development. We find that the requirement for Wnt/beta-catenin signaling extends throughout the pronephric primordium and is essential for the development of proximal and distal tubules of the pronephros as well as for the development of the duct and glomus. Although less pronounced than effects upon later pronephric tubule differentiation, inhibition of the Wnt/beta-catenin pathway decreased expression of early pronephric mesenchymal markers indicating it is also needed in early pronephric patterning. We find that upstream inhibition of Wnt/beta-catenin signals in zebrafish likewise reduces pronephric epithelial tubulogenesis. We also find that exogenous activation of Wnt/beta-catenin signaling within the Xenopus pronephric field results in significant tubulogenic losses. Together, we propose Wnt/beta-catenin signaling is required for pronephric tubule, duct and glomus formation in Xenopus laevis, and this requirement is conserved in zebrafish pronephric tubule formation.
机译:在早期鱼类和两栖动物胚胎发生期间,前肾控制水和电解质的平衡。许多Wnt信号传导成分与肾脏发育有关。具体而言,在非洲爪蟾前肾发育以及鼠后肾中,分泌的糖蛋白Wnt-4已被证明对肾小管形成至关重要。尽管Wnt信号在肾脏器官发生中具有重要意义,但对介导其作用的确定性下游信号传导途径知之甚少。在这里我们报告说,非洲爪蟾前肾区域内Wnt /β-catenin信号的抑制导致肾脏上皮小管生成的重大损失,而对相邻轴或so突发育几乎没有影响。我们发现,Wnt /β-catenin信号的需求遍及整个前肾原基,对于前肾近端和远端小管的发育以及导管和阴茎的发育至关重要。尽管对后期肾小管分化的影响不那么明显,但对Wnt /β-catenin途径的抑制降低了早期肾原间充质标记的表达,表明在早期肾原性模式中也需要它。我们发现上游抑制斑马鱼中的Wnt /β-catenin信号同样减少前肾上皮小管生成。我们还发现,非洲爪蟾前肾野内Wnt /β-catenin信号的外源性激活导致显着的微管生成损失。在一起,我们建议非洲爪蟾的前肾小管,管道和glomus形成需要Wnt /β-catenin信号,并且在斑马鱼前肾小管形成中保持这一要求。

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