Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 12, Pages 4640-4645Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1213971110
Keywords
cap mesenchyme; niche; pretubular aggregate; nephrogenic zone; kidney development
Categories
Funding
- National Institutes of Diabetes and Digestive and Kidney Disease (NIDDK) [R01DK078161]
- American Recovery and Reinvestment Act-supported supplement Grant [R01DK078161]
- American Heart Association
- NIDDK [F32DK093195]
- National Institutes of General Medicine (NIGM) [8P20 GM103465]
- Histopathology by NIGM [8P20 GM103465, 8P30 GM103392]
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Embryonic nephron progenitor cells are segregated in molecularly distinct compartments of unknown function. Our study reveals an integral role for bone morphogenetic protein-SMAD in promoting transition of progenitors from the primitive Cbp/p300-interacting transactivator 1 expressing (CITED1+) compartment to the uniquely sine oculis-related homeobox 2 expressing (SIX2-only) compartment where they become inducible by wingless-type mouse mammary tumor virus integration site family member (WNT)/beta-catenin signaling. Significantly, CITED1(+) cells are refractory to WNT/beta-catenin induction. We propose a model in which the primitive CITED1(+) compartment is refractory to induction by WNT9b/beta-catenin, ensuring maintenance of undifferentiated progenitor cells for future nephrogenesis. Bone morphogenetic protein 7-SMAD is then required for transition to a distinct compartment in which cells become inducible by WNT9b/beta-catenin, allowing them to progress toward epithelialization.
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