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

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          Abstract

          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.

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          Author and article information

          Journal
          Cell Stem Cell
          Cell stem cell
          Elsevier BV
          1875-9777
          1875-9777
          Aug 07 2008
          : 3
          : 2
          Affiliations
          [1 ] Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.
          Article
          S1934-5909(08)00347-0 NIHMS53557
          10.1016/j.stem.2008.05.020
          2561900
          18682239
          21ec3b7d-27d3-4015-ab27-f29ab1ea9d52
          History

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