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Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
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Prorenin receptor is critical for nephron progenitors
Renfang Song1, Graeme Preston1, Laura Kidd1
1Department of Pediatrics, Department of Pathology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Developmental Biology
|December 15, 2015
Summary
The prorenin receptor (PRR) is crucial for kidney development. Its absence in nephron progenitors leads to severe kidney defects and early death in mice, highlighting PRR
Area of Science:
- Developmental Biology
- Nephrology
- Molecular Biology
Background:
- Renal hypoplasia, characterized by small kidneys, stems from deficient nephrogenesis.
- Nephron induction involves interactions between cap mesenchyme (CM) and ureteric bud (UB).
- The prorenin receptor (PRR) is vital for blood pressure regulation and cellular functions.
Purpose of the Study:
- To investigate the role of the prorenin receptor (PRR) in nephrogenesis.
- To circumvent the lethality of global PRR mutations in mice.
- To determine the cell-autonomous function of PRR in nephron progenitors.
Main Methods:
- Generated a conditional knockout mouse model with PRR deleted in Six2(+) nephron progenitors (Six2(PRR-/-)).
- Analyzed kidney development, progenitor cell populations, and molecular signaling pathways.
- Assessed kidney function, histology, and proteinuria in mutant and heterozygous mice.
Main Results:
- Targeted PRR ablation in nephron progenitors caused reduced nephron numbers, small cystic kidneys, and early death.
- PRR deficiency led to premature depletion of nephron progenitor cells and impaired Wnt/β-catenin signaling.
- Heterozygous mice (Six2(PRR+/-)) developed focal glomerulosclerosis, kidney dysfunction, and proteinuria.
Conclusions:
- The prorenin receptor (PRR) is essential for maintaining nephron progenitor cells.
- PRR is cell-autonomously required for normal kidney development and function.
- Impaired PRR signaling in progenitors disrupts nephrogenesis and leads to kidney disease.
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