title: Pronephric tubulogenesis requires Daam1-mediated planar cell polarity signaling.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Miller
authors.forename: Sol Gomez de la Torre
authors.initials: SG
authors.lastname: Canny
authors.forename: Chuan-Wei
authors.initials: CW
authors.lastname: Jang
authors.forename: Kyucheol
authors.initials: K
authors.lastname: Cho
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Wagner
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Jones
authors.forename: Raymond
authors.initials: R
authors.lastname: Habas
authors.forename: Pierre D
authors.initials: PD
authors.lastname: McCrea
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D016764:Cell Polarity; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000378:metabolism*; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D007684:Kidney Tubules / Q000196:embryology*; D038081:Organogenesis; D051153:Wnt Proteins / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C443939:Daam1 protein, Xenopus; D020662:Guanine Nucleotide Exchange Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins