Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4

Nature. 1994 Dec 15;372(6507):679-83. doi: 10.1038/372679a0.


The kidney has been widely exploited as a model system for the study of tissue inductions regulating vertebrate organogenesis. Kidney development is initiated by the ingrowth of the Wolfian duct-derived ureteric bud into the presumptive kidney mesenchyme. In response to a signal from the ureter, mesenchymal cells condense, aggregate into pretubular clusters and undergo an epithelial conversion generating a simple tubule. This then undergoes morphogenesis and is transformed into the excretory system of the kidney, the nephron. We report here that the expression of Wnt-4, which encodes a secreted glycoprotein, correlates with, and is required for, kidney tubulogenesis. Mice lacking Wnt-4 activity fail to form pretubular cell aggregates; however, other aspects of mesenchymal and ureteric development are unaffected. Thus, Wnt-4 appears to act as an autoinducer of the mesenchyme to epithelial transition that underlies nephron development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Adhesion / physiology
  • Cell Line
  • Chick Embryo
  • DNA
  • DNA-Binding Proteins / genetics
  • Embryonic Induction* / genetics
  • Gene Expression
  • Gene Targeting
  • Genes, Wilms Tumor
  • Genetic Markers
  • Kidney Tubules / anatomy & histology
  • Kidney Tubules / embryology*
  • Mesoderm / physiology
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins*
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Stem Cells
  • Trans-Activators / genetics
  • Ureter / embryology
  • Ureter / physiology
  • Wnt Proteins
  • Wnt4 Protein


  • DNA-Binding Proteins
  • Genetic Markers
  • Nuclear Proteins
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors
  • Pax8 protein, mouse
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Wnt Proteins
  • Wnt4 Protein
  • Wnt4 protein, mouse
  • DNA