title: Canonical WNT signaling during kidney development.
abstract: The canonical WNT signaling pathway plays a crucial role in patterning of the embryo during development, but little is known about the specific developmental events which are under WNT control. To understand more about how the WNT pathway orchestrates mammalian organogenesis, we studied the canonical beta-catenin-mediated WNT signaling pathway in kidneys of mice bearing a beta-catenin-responsive TCF/betaGal reporter transgene. In metanephric kidney, intense canonical WNT signaling was evident in epithelia of the branching ureteric bud and in nephrogenic mesenchyme during its transition into renal tubules. WNT signaling activity is rapidly downregulated in maturing nephrons and becomes undetectable in postnatal kidney. Sites of TCF/betaGal activity are in proximity to the known sites of renal WNT2b and WNT4 expression, and these WNTs stimulate TCF reporter activity in kidney cell lines derived from ureteric bud and metanephric mesenchyme lineages. When fetal kidney explants from HoxB7/GFP mice were exposed to the canonical WNT signaling pathway inhibitor, Dickkopf-1, arborization of the ureteric bud was significantly reduced. We conclude that restricted zones of intense canonical WNT signaling drive branching nephrogenesis in fetal kidney.
authors.affiliation: Department of Human Genetics, McGill University-Montreal Children's Hospital Research Institute, 4060 St. Catherine West, Montreal, QC, Canada H3Z 2Z3.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Iglesias
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Hueber
authors.forename: LeeLee
authors.initials: L
authors.lastname: Chu
authors.forename: Robert
authors.initials: R
authors.lastname: Campbell
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Patenaude
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Dziarmaga
authors.forename: Jacklyn
authors.initials: J
authors.lastname: Quinlan
authors.forename: Othman
authors.initials: O
authors.lastname: Mohamed
authors.forename: Daniel
authors.initials: D
authors.lastname: Dufort
authors.forename: Paul R
authors.initials: PR
authors.lastname: Goodyer
mesh_terms: D000818:Animals; D002460:Cell Line; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000196:embryology* / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D050809:POU Domain Factors / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D014513:Ureter / Q000196:embryology; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C501126:DKK1 protein, human; D018076:DNA, Complementary; D036341:Intercellular Signaling Peptides and Proteins; D050809:POU Domain Factors; C082703:POU6F1 protein, human; D051153:Wnt Proteins; D051176:beta Catenin