Requirement of Wnt/beta-catenin signaling in pronephric kidney development.
Requirement of Wnt/beta-catenin signaling in pronephric kidney development.
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Wnt/β-catenin信号在俯卧肾发育中的需求。
DOI：
10.1016/j.mod.2008.11.007
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发表时间：
2009-03
影响因子：
2.6
通讯作者：
McCrea, Pierre D.
中科院分区：
文献类型：
--
作者：
Lyons, Jon P.;Miller, Rachel K.;Zhou, Xiaolan;Weidinger, Gilbert;Deroo, Tom;Denayer, Tinneke;Park, Jae-Il;Ji, Hong;Hong, Ji Yeon;Li, Annette;Moon, Randall T.;Jones, Elizabeth A.;Vleminckx, Kris;Vize, Peter D.;McCrea, Pierre D.
前肾在鱼类和两栖动物胚胎发生早期控制水和电解质平衡。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发育中，分泌的糖蛋白 Wnt-4 已被证明对于肾小管形成至关重要。尽管 Wnt 信号在肾脏器官发生中很重要，但介导其作用的明确下游信号通路却知之甚少。在这里，我们报告抑制非洲爪蟾前肾区内的 Wnt/β-连环蛋白信号传导会导致肾上皮肾小管发生的显着损失，而对相邻轴或体节发育影响很小或没有影响。我们发现对 Wnt/β-连环蛋白信号传导的需求延伸到整个前肾原基，并且对于前肾近端和远端小管的发育以及导管和血管球的发育至关重要。虽然不如对后来的前肾小管分化的影响明显，但抑制 Wnt/β-连环蛋白途径会降低早期前肾间充质标志物的表达，表明早期前肾模式化也需要它。我们发现斑马鱼中 Wnt/β-连环蛋白信号的上游抑制同样会减少前肾上皮小管的发生。我们还发现非洲爪蟾前肾区 Wnt/β-catenin 信号传导的外源激活会导致显着的肾小管发生损失。总之，我们提出Wnt/β-连环蛋白信号是非洲爪蟾前肾小管、导管和血管球形成所必需的，并且这种要求在斑马鱼前肾小管形成中是保守的。
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/β-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/β-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/β-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/β-catenin signals in zebrafish likewise reduces pronephric epithelial tubulogenesis. We also find that exogenous activation of Wnt/β-catenin signaling within the Xenopus pronephric field results in significant tubulogenic losses. Together, we propose Wnt/β-catenin signaling is required for pronephric tubule, duct and glomus formation in Xenopus laevis, and this requirement is conserved in zebrafish pronephric tubule formation.
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