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

By Akio Kobayashi, M. Valerius, Joshua W. Mugford, Thomas J. Carroll, M. Self, G. Oliver, Andrew P. McMahon. Cell Stem Cell, 2008

946 citations recorded by the source corpus.

SUMMARY 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 is 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.

Subfields: Genetics, Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/6e8e8b918d18f1d166788c487b04dee67d75d94a

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Citations in the corpus

Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells. (2014, methodology): “We further crossed Six2-GFPCreER mice (Kobayashi et al., 2008) with mice carrying a tdTomato reporter allele (Madisen et al.”
Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. (2010, methodology): “In the Six2-Cre transgenic mouse, expression of Cre occurs in cap-mesenchyme and labels all non-ureteric, bud-derived, nephron epithelia, including podocytes, proximal tubule, loop of Henle, and connecting segment, but it does not label any interstitial cell population.(34,38) FoxD1 is a well charac”
Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development (2010, positive): “To generate this large number of nephrons, Cited1, Six2 cells undergo at least four rounds of replicative divisions from E11 to birth in the mouse to expand !16 fold (Kobayashi et al., 2008).”