Inversin relays Frizzled-8 signals to promote proximal pronephros development

Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20388-93. doi: 10.1073/pnas.1013070107. Epub 2010 Nov 8.


Mutations of inversin cause type II nephronophthisis, an infantile autosomal recessive disease characterized by cystic kidney disease and developmental defects. Inversin regulates Wnt signaling and is required for convergent extension movements during early embryogenesis. We now show that Inversin is essential for Xenopus pronephros formation, involving two distinct and opposing forms of cell movements. Knockdown of Inversin abrogated both proximal pronephros extension and distal tubule differentiation, phenotypes similar to that of Xenopus deficient in Frizzled-8. Exogenous Inversin rescued the pronephric defects caused by lack of Frizzled-8, indicating that Inversin acts downstream of Frizzled-8 in pronephros morphogenesis. Depletion of Inversin prevents the recruitment of Dishevelled in response to Frizzled-8 and impeded the accumulation of Dishevelled at the apical membrane of tubular epithelial cells in vivo. Thus, defective tubule morphogenesis seems to contribute to the renal pathology observed in patients with nephronophthisis type II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Dishevelled Proteins
  • Fluorescence
  • In Situ Hybridization
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kidney / embryology*
  • Kidney / metabolism
  • Mice
  • Microscopy, Confocal
  • Oligonucleotides / genetics
  • Phosphoproteins / metabolism
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction / physiology*
  • Transcription Factors / metabolism*
  • Wnt Proteins / metabolism
  • Xenopus
  • Xenopus Proteins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Dishevelled Proteins
  • FZD8 protein, Xenopus
  • Intracellular Signaling Peptides and Proteins
  • Invs protein, Xenopus
  • Oligonucleotides
  • Phosphoproteins
  • Receptors, Cell Surface
  • Transcription Factors
  • Wnt Proteins
  • Xenopus Proteins