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Am J Physiol Renal Physiol 293: F494-F500, 2007. First published May 9, 2007; doi:10.1152/ajprenal.00416.2006
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Canonical WNT signaling during kidney development

Diana M. Iglesias,1 Pierre-Alain Hueber,2 LeeLee Chu,3 Robert Campbell,3 Anne-Marie Patenaude,3 Alison J. Dziarmaga,1 Jacklyn Quinlan,1 Othman Mohamed,4 Daniel Dufort,4 and Paul R. Goodyer1,2,3

1Department of Human Genetics, 2Department of Experimental Medicine, 3Department of Pediatrics, McGill University-Montreal Children's Hospital Research Institute, 4Department of Obstetrics and Gynecology, McGill University Health Centre Research Institute and McGill University, Montreal, Quebec, Canada

Submitted 20 October 2006 ; accepted in final form 3 May 2007

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.

nephrogenesis; beta-catenin; branching morphogenesis


Address for reprint requests and other correspondence: P. Goodyer, Montreal Children's Hospital Research Institute, 4060 St. Catherine West, Montreal, QC, Canada H3Z 2Z3 (e-mail: Paul.Goodyer{at}mcgill.ca)




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