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Dev Biol. 2018 Aug 1;440(1):13-21. doi: 10.1016/j.ydbio.2018.04.020. Epub 2018 Apr 26.

Disparate levels of beta-catenin activity determine nephron progenitor cell fate.

Author information

1
Departments of Internal Medicine (Nephrology), University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9148, USA; Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9148, USA.
2
Renal Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
3
Department of Internal Medicine, Saint Louis University, St Louis, MO 63104, USA; Department of Biochemistry and Molecular Biology, Saint Louis University, St Louis, MO 63104, USA; VA St. Louis Health Care System, John Cochran Division, St Louis, MO 63106, USA.
4
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074, USA.
5
Department of Stem Cell Biology and Regenerative Medicine, W.M. Keck School of Medicine of the University of Southern California,1425 San Pablo Street, Los Angeles, CA 90033, USA; 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.
6
Departments of Internal Medicine (Nephrology), University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9148, USA; Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9148, USA. Electronic address: thomas.carroll@utsouthwestern.edu.

Abstract

Formation of a functional kidney depends on the balance between renewal and differentiation of nephron progenitors. Failure to sustain this balance can lead to kidney failure or stem cell tumors. For nearly 60 years, we have known that signals from an epithelial structure known as the ureteric bud were essential for maintaining this balance. More recently it was discovered that one molecule, Wnt9b, was necessary for both renewal and differentiation of the nephron progenitor cells. How one ligand signaling through one transcription factor promoted two seemingly contradictory cellular processes was unclear. In this study, we show that Wnt9b/beta-catenin signaling alone is sufficient to promote both renewal and differentiation. Moreover, we show that discrete levels of beta-catenin can promote these two disparate fates, with low levels fostering progenitor renewal and high levels driving differentiation. These results provide insight into how Wnt9b regulates distinct target genes that balance nephron progenitor renewal and differentiation.

PMID:
29705331
PMCID:
PMC5988999
DOI:
10.1016/j.ydbio.2018.04.020
[Indexed for MEDLINE]
Free PMC Article

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