Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4.
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.
Stark
K
K
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138.
Vainio
S
S
Vassileva
G
G
McMahon
A P
AP
D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002642:Chick Embryo; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics; D004627:Embryonic Induction / Q000235:genetics; D015870:Gene Expression; D018390:Gene Targeting; D016162:Genes, Wilms Tumor; D005819:Genetic Markers; D007684:Kidney Tubules / Q000033:anatomy & histology / Q000196:embryology*; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells; D015534:Trans-Activators / Q000235:genetics; D014513:Ureter / Q000196:embryology / Q000502:physiology; D051153:Wnt Proteins; D060528:Wnt4 Protein
D004268:DNA-Binding Proteins; D005819:Genetic Markers; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499496:Pax8 protein, mouse; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; D004247:DNA