Canonical WNT signaling during kidney development

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 canonica...

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Bibliographic Details
Published in:American journal of physiology. Renal physiology 2007-08, Vol.293 (2), p.F494-F500
Main Authors: Iglesias, Diana M, Hueber, Pierre-Alain, Chu, LeeLee, Campbell, Robert, Patenaude, Anne-Marie, Dziarmaga, Alison J, Quinlan, Jacklyn, Mohamed, Othman, Dufort, Daniel, Goodyer, Paul R
Format: Article
Language:English
Subjects:
Animals
beta Catenin - metabolism
Cell Line
DNA, Complementary - biosynthesis
DNA, Complementary - genetics
Down-Regulation - physiology
Embryology
Epithelial Cells - physiology
Gene expression
Genes
Genes, Reporter - genetics
Humans
Immunohistochemistry
Intercellular Signaling Peptides and Proteins - metabolism
Kidney - embryology
Kidney - metabolism
Kidney Tubules, Collecting - metabolism
Kidneys
Lac Operon - genetics
Mice
Mice, Transgenic
Microscopy, Fluorescence
POU Domain Factors - genetics
Rodents
Signal Transduction - physiology
Transfection
Ureter - embryology
Wnt Proteins - physiology
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Summary: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.
ISSN:1931-857X
1522-1466
DOI:10.1152/ajprenal.00416.2006