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Abstract: SA-PO554

Loss of the Planar Cell Polarity Gene Fuzzy Leads to Defective Branching Morphogenesis and Cystogenesis in Embryonic Kidneys

Session Information

  • Developmental Biology
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Developmental Biology and Inherited Kidney Diseases

  • 401 Developmental Biology


  • Wang, Yanran, McGill University, Montreal, Quebec, Canada
  • Torban, Elena, McGill University, Montreal, Quebec, Canada

The PCP effector gene Fuzzy is essential for organogenesis. In Drosophila, it is critical for establishing planar cell polarity via controlling the actin cytoskeleton. In vertebrates, the role of Fuzzy is less clear, but it appears to control some aspects of trafficking protein cargos to the basal body. Fuzzy has been designated as a Ciliogenesis and PCP effector (CPLANE) gene. Disruption of Fuzzy in mice results in severe malformations, including neural tube defects, polydactyly, facial defects andetc, suggesting its participation in various signaling pathways.


To study kidney development, homozygous E14.5 and E16.5 embryos carrying a gene-trap Fuzzy mutation and wildtype littermates were harvested for immunofluorescense and in situ hybridization (ISH) studies.


Fuzzy-/- mutants exhibited profound renal hypoplasia at E14.5. Although Six2-positive progenitor cells and their differentiation into early nephron structures were unaffected, the number of the ureteric buds was decreased to 50% of control. This was accompanied by a ~ 50% reduction in the number of glomeruli without a decrease in the number of podocytes per glomerulus. ISH studies indicated that GDNF expression was unaffected, but c-Ret expression was upregulated in Fuzzy-/- mutants. The expression of the Hippo kinase pathway effector Yap was decreased significantly in ureteric buds. At E16.5, Fuzzy-/- mutants exhibited glomerular cysts in the medullary layer, manifested by the dilation of Bowman’s capsule. E16.5 Fuzzy-/- mutants also developed proximal tubular cysts but collecting ducts remained intact.


Impaired UB branching is a major cause of renal hypoplasia in E14.5 Fuzzy-/- mice and is associated with increased Ret signaling and a decrease in Yap expression in the UBs. This phenotype is reminiscent of the phenotype of Yap mutants, suggesting that Fuzzy may participate in Hippo signaling pathway. The mechanisms of glomerular and proximal tubular cysts formation are being investigated.


  • Government Support - Non-U.S.