Wnt9b signaling regulates planar cell polarity and kidney tubule morphogenesis.
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.
Karner
Courtney M
CM
Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Chirumamilla
Rani
R
Aoki
Shigehisa
S
Igarashi
Peter
P
Wallingford
John B
JB
Carroll
Thomas J
TJ
D000818:Animals; D016764:Cell Polarity; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000166:cytology / Q000254:growth & development; D007684:Kidney Tubules / Q000166:cytology / Q000254:growth & development*; D008297:Male; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
D051153:Wnt Proteins; C515303:Wnt9b protein, mouse