Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney

Michelle Self, Oleg V. Lagutin, Beth Bowling, Jaime Hendrix, Yi Cai, Gregory R. Dressler, Guillermo Oliver*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

318 Scopus citations

Abstract

During kidney development and in response to inductive signals, the metanephric mesenchyme aggregates, becomes polarized, and generates much of the epithelia of the nephron. As such, the metanephric mesenchyme is a renal progenitor cell population that must be replenished as epithelial derivatives are continuously generated. The molecular mechanisms that maintain the undifferentiated state of the metanephric mesenchymal precursor cells have not yet been identified. In this paper, we report that functional inactivation of the homeobox gene Six2 results in premature and ectopic differentiation of mesenchymal cells into epithelia and depletion of the progenitor cell population within the metanephric mesenchyme. Failure to renew the mesenchymal cells results in severe renal hypoplasia. Gain of Six2 function in cortical metanephric mesenchymal cells was sufficient to prevent their epithelial differentiation in an organ culture assay. We propose that in the developing kidney, Six2 activity is required for maintaining the mesenchymal progenitor population in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud.

Original languageEnglish (US)
Pages (from-to)5214-5228
Number of pages15
JournalEMBO Journal
Volume25
Issue number21
DOIs
StatePublished - Nov 1 2006

Keywords

  • Homeobox
  • Kidney
  • Mouse
  • Nephrogenesis
  • Six2

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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