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Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development.

Nephrons, the basic functional units of the kidney, are generated repetitively during kidney organogenesis from a mesenchymal progenitor population. Which cells within this pool give rise to nephrons and how multiple nephron lineages form during this protracted developmental process are unclear. We demonstrate that the Six2-expressing cap mesenchyme represents a multipotent nephron progenitor population. Six2-expressing cells give rise to all cell types of the main body of the nephron during all stages of nephrogenesis. Pulse labeling of Six2-expressing nephron progenitors at the onset of kidney development suggests that the Six2-expressing population is maintained by self-renewal. Clonal analysis indicates that at least some Six2-expressing cells are multipotent, contributing to multiple domains of the nephron. Furthermore, Six2 functions cell autonomously to maintain a progenitor cell status, as cap mesenchyme cells lacking Six2 activity contribute to ectopic nephron tubules, a mechanism dependent on a Wnt9b inductive signal. Taken together, our observations suggest that Six2 activity cell-autonomously regulates a multipotent nephron progenitor population.

Pubmed ID: 18682239


  • Kobayashi A
  • Valerius MT
  • Mugford JW
  • Carroll TJ
  • Self M
  • Oliver G
  • McMahon AP


Cell stem cell

Publication Data

August 7, 2008

Associated Grants

  • Agency: NCI NIH HHS, Id: CA-21765
  • Agency: NIDDK NIH HHS, Id: DK054364
  • Agency: NIDDK NIH HHS, Id: F32 DK060319-03
  • Agency: NIDDK NIH HHS, Id: F32DK060319
  • Agency: NIDDK NIH HHS, Id: R01 DK054364
  • Agency: NIDDK NIH HHS, Id: R01 DK054364-10

Mesh Terms

  • Animals
  • Cell Differentiation
  • Chimera
  • Homeodomain Proteins
  • Immunohistochemistry
  • Kidney
  • Mesenchymal Stromal Cells
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Nephrons
  • Organogenesis
  • Transcription Factors
  • Transcriptional Activation
  • Wnt Proteins