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J Am Soc Nephrol September 1, 2011; 22 (9): 1654-64.

Pronephric tubulogenesis requires Daam1-mediated planar cell polarity signaling.

Miller RK , Canny SG , Jang CW , Cho K , Ji H , Wagner DS , Jones EA , Habas R , McCrea PD .

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.

PubMed ID: 21804089
PMC ID: PMC3171937
Article link: J Am Soc Nephrol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: actl6a arhgef19 clock ctnnb1 daam1 fat4 invs rho rho.2 vangl2 wnt11 wnt11b wnt4 wnt5a wnt6 wnt7b wnt8a wnt8b wnt9a wnt9b
Antibodies: H3f3a Ab9 Kidney Ab1 Kidney Ab2 Somite Ab1
Morpholinos: arhgef19 MO2 daam1 MO1

References [+] :
Agrawal, The miR-30 miRNA family regulates Xenopus pronephros development and targets the transcription factor Xlim1/Lhx1. 2009, Pubmed, Xenbase