The Wnt/JNK signaling target gene alcam is required for embryonic kidney development.
Proper development of nephrons is essential for kidney function. β-Catenin-independent Wnt signaling through Fzd8, Inversin, Daam1, RhoA and Myosin is required for nephric tubule morphogenesis. Here, we provide a novel mechanism through which non-canonical Wnt signaling contributes to tubular development. Using Xenopus laevis as a model system, we found that the cell-adhesion molecule Alcam is required for proper nephrogenesis and functions downstream of Fzd3 during embryonic kidney development. We found alcam expression to be independent of Fzd8 or Inversin, but to be transcriptionally regulated by the β-Catenin-independent Wnt/JNK pathway involving ATF2 and Pax2 in a direct manner. These novel findings indicate that several branches of Wnt signaling are independently required for proximal tubule development. Moreover, our data indicate that regulation of morphogenesis by non-canonical Wnt ligands also involves direct transcriptional responses in addition to the effects on a post-translational level.
Institute for Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, Ulm 89081, Germany.
Wiebke
W
Cizelsky
Aleksandra
A
Tata
Michael
M
Kühl
Susanne J
SJ
Kühl
D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000235:genetics / Q000502:physiology*; D000818:Animals; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000235:genetics*; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000196:embryology* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics*; D051762:PAX2 Transcription Factor / Q000502:physiology; D060910:Pronephros / Q000196:embryology / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics
D020410:Activated-Leukocyte Cell Adhesion Molecule; C486340:FZD3 protein, Xenopus; D051157:Frizzled Receptors; D051762:PAX2 Transcription Factor; D029867:Xenopus Proteins
DM-GRASP; Kidney; Pronephros; Xenopus laevis; alcam