Article abstract


Nature Genetics 41, 793 - 799 (2009)
Published online: 21 June 2009 | doi:10.1038/ng.400

Wnt9b signaling regulates planar cell polarity and kidney tubule morphogenesis

Courtney M Karner1,2, Rani Chirumamilla1,2, Shigehisa Aoki1,3, Peter Igarashi1,4, John B Wallingford5 & Thomas J Carroll1,2


Although many vertebrate organs, such as kidneys, lungs and liver, are composed of epithelial tubules, little is known of the mechanisms that establish the length or diameter of these tubules. In the kidney, defects in the establishment or maintenance of tubule diameter are associated with one of the most common inherited human disorders, polycystic kidney disease. Here we show that attenuation of Wnt9b signaling during kidney morphogenesis affects the planar cell polarity of the epithelium and leads to tubules with significantly increased diameter. Although previous studies showed that polarized cell divisions maintain the diameter of postnatal kidney tubules, we find that cell divisions are randomly oriented during embryonic development. Our data suggest that diameter is established during early morphogenetic stages by convergent extension processes and maintained by polarized cell divisions. Wnt9b, signaling through the non-canonical Rho/Jnk branch of the Wnt pathway, is necessary for both of these processes.

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  1. Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
  2. Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
  3. Pathology & Biodefense Faculty of Medicine, Saga University, Saga, Japan.
  4. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
  5. Molecular, Cell and Developmental Biology & Institute for Cellular and Molecular Biology, University of Texas, Austin, Austin, Texas, USA.

Correspondence to: Thomas J Carroll1,2 e-mail: thomas.carroll@utsouthwestern.edu



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