Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
J Am Soc Nephrol. 2011 Sep;22(9):1654-64. doi: 10.1681/ASN.2010101086. Epub 2011 Jul 29.
Canonical β-catenin-mediated Wnt signaling is essential for the induction of nephron development. Noncanonical Wnt/planar cell polarity (PCP) pathways contribute to processes such as cell polarization and cytoskeletal modulation in several tissues. Although PCP components likely establish the plane of polarization in kidney tubulogenesis, whether PCP effectors directly modulate the actin cytoskeleton in tubulogenesis is unknown. Here, we investigated the roles of Wnt PCP components in cytoskeletal assembly during kidney tubule morphogenesis in Xenopus laevis and zebrafish. We found that during tubulogenesis, the developing pronephric anlagen expresses Daam1 and its interacting Rho-GEF (WGEF), which compose one PCP/noncanonical Wnt pathway branch. Knockdown of Daam1 resulted in reduced expression of late pronephric epithelial markers with no apparent effect upon early markers of patterning and determination. Inhibiting various points in the Daam1 signaling pathway significantly reduced pronephric tubulogenesis. These data indicate that pronephric tubulogenesis requires the Daam1/WGEF/Rho PCP pathway.
规范的 β-连环蛋白介导的 Wnt 信号通路对于诱导肾单位发育是必需的。非规范的 Wnt/平面细胞极性（PCP）途径有助于几个组织中的细胞极化和细胞骨架调节等过程。尽管 PCP 成分可能在肾单位发生中建立极化平面，但 PCP 效应物是否直接调节肾单位发生中的肌动蛋白细胞骨架尚不清楚。在这里，我们研究了 Wnt PCP 成分在 Xenopus laevis 和斑马鱼肾脏小管形态发生过程中细胞骨架组装中的作用。我们发现，在小管发生过程中，发育中的前肾原基表达 Daam1 和与其相互作用的 Rho-GEF（WGEF），它们构成 PCP/非规范 Wnt 途径的一个分支。Daam1 的敲低导致晚期前肾上皮标志物的表达减少，而对模式和决定的早期标志物没有明显影响。抑制 Daam1 信号通路的各个点显著降低了前肾小管发生。这些数据表明，前肾小管发生需要 Daam1/WGEF/Rho PCP 途径。
