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08:06
Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
p53 regulates metanephric development
Zubaida Saifudeen1, Susana Dipp, Jana Stefkova
1Section of Pediatric Nephrology, Department of Pediatrics, and the Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA 70112, USA. zubisaif@tulane.edu
Journal of the American Society of Nephrology : JASN
|September 5, 2009
Summary
The tumor suppressor p53 (protein 53) normally restricts ureteric bud (UB) outgrowth from the Wolffian duct (WD). Loss of p53 causes congenital kidney abnormalities, including ectopic UB budding.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- The tumor suppressor protein p53 (p53) is crucial for cell cycle regulation, differentiation, and apoptosis.
- Its role in embryonic development and organogenesis, particularly kidney development, is not fully understood.
Purpose of the Study:
- To investigate the role of p53 in embryonic kidney development and organogenesis.
- To elucidate the mechanisms by which p53 influences ureteric bud (UB) outgrowth and kidney formation.
Main Methods:
- Generation and analysis of p53 knockout (p53(-/-)) mouse embryos.
- Ex vivo organ culture of embryonic kidneys.
- Transgenic expression of dominant-negative p53 and conditional inactivation of p53 in specific cell lineages (UB and metanephric mesenchyme).
- Analysis of signaling pathways, including glial cell line-derived neurotrophic factor (GDNF) and phosphatidylinositol-3 kinase (PI3K).
Main Results:
- p53(-/-) embryos display a range of congenital kidney and urinary tract abnormalities, including ureteric bud ectopia, duplex systems, and hypoplastic kidneys.
- Ectopic UB outgrowth from the Wolffian duct (WD) was observed in a significant portion of p53(-/-) embryos.
- Conditional inactivation of p53 in the UB, but not the metanephric mesenchyme, recapitulated the duplex phenotype.
- p53 inactivation in the WD leads to enhanced sensitivity to GDNF-induced ectopic budding and potentiated PI3K activation by GDNF.
Conclusions:
- p53 plays a critical restrictive role in regulating ureteric bud outgrowth from the Wolffian duct during kidney development.
- Loss of p53 function results in aberrant UB budding, leading to congenital abnormalities of the kidney and urinary tract.
- The findings highlight a novel function of p53 in preventing ectopic UB development mediated by GDNF signaling.
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