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Dev Cell. 2017 May 22;41(4):349-365.e3. doi: 10.1016/j.devcel.2017.04.022.

Repression of Interstitial Identity in Nephron Progenitor Cells by Pax2 Establishes the Nephron-Interstitium Boundary during Kidney Development.

Author information

1
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
2
Department of Medicine, Institute for Stem Cell and Regenerative Medicine, University of Washington, 750 Republican Street, Seattle, WA 98109, USA.
3
Division of Developmental Biology, Cincinnati Children's Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
4
Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, W.M. Keck School of Medicine of the University of Southern California, 1425 San Pablo Street, Los Angeles, CA 90033, USA.
5
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA; Department of Medicine, Institute for Stem Cell and Regenerative Medicine, University of Washington, 750 Republican Street, Seattle, WA 98109, USA. Electronic address: akiok@uw.edu.

Abstract

The kidney contains the functional units, the nephrons, surrounded by the renal interstitium. Previously we discovered that, once Six2-expressing nephron progenitor cells and Foxd1-expressing renal interstitial progenitor cells form at the onset of kidney development, descendant cells from these populations contribute exclusively to the main body of nephrons and renal interstitial tissues, respectively, indicating a lineage boundary between the nephron and renal interstitial compartments. Currently it is unclear how lineages are regulated during kidney organogenesis. We demonstrate that nephron progenitor cells lacking Pax2 fail to differentiate into nephron cells but can switch fates into renal interstitium-like cell types. These data suggest that Pax2 function maintains nephron progenitor cells by repressing a renal interstitial cell program. Thus, the lineage boundary between the nephron and renal interstitial compartments is maintained by the Pax2 activity in nephron progenitor cells during kidney organogenesis.

KEYWORDS:

FOXD1; PAX2; SIX2; cell fate; interstitium; kidney; lineage boundary; nephron; progenitor

PMID:
28535371
PMCID:
PMC5532731
DOI:
10.1016/j.devcel.2017.04.022
[Indexed for MEDLINE]
Free PMC Article

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