Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 793-799 |
| Number of pages | 7 |
| Journal | Nature Genetics |
| Volume | 41 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2009 |
Bibliographical note
Funding Information:We thank O. Cleaver for reading and commenting on this manuscript, L. Avery for help with statistical analysis, J. Zhou (Brigham and Women’s and Harvard Medical School) for providing us with antibodies to Pc-1 and Pc-2 and the Pkd1 mutant kidneys, M. Taketo (Kyoto University) for providing the beta-catenin exon 3 flox mice, O. Cabello (J.H. Quillen College of Medicine, East Tennessee State University) for providing us with the Invs mutant kidneys, B. Adams, E. Small, J. Shelton and the Molecular Pathology Core for technical assistance and L. James and M. Princena for the urine albumin studies. This work was supported by grants from the American Society for Nephrology, the American Heart Association (0730236N), the Polycystic Kidney Disease Research Foundation, the UAB ARPKD Center (5P30DK07403802) and the US National Institutes of Health (1R01DK080004) to T.J.C. The work was also supported by the University of Texas Southwestern O’Brien Kidney Research Core Center (NIH P30DK079328). J.B.W. was supported by grants from the National Institute for General Medical Sciences, the March of Dimes and the Burroughs Wellcome Fund.
