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Brg1 determines urothelial cell fate during ureter development
Robert M Weiss1, Songshan Guo, Alan Shan
1Department of Urology, Yale University School of Medicine, New Haven, CT 06520, USA.
Journal of the American Society of Nephrology : JASN
|March 2, 2013
Summary
The epigenetic regulator Brg1 is crucial for ureter development, controlling urothelial cell differentiation and smooth muscle development. Loss of Brg1 impairs ureter formation, leading to conditions like hydroureter.
Area of Science:
- Developmental Biology
- Epigenetics
- Urology
Background:
- The epigenetic regulator Brg1 (also known as SMARCA4) is expressed in developing and adult ureters.
- Its specific role in ureter development remains largely unknown.
Purpose of the Study:
- To investigate the function of Brg1 in the developing ureter.
- To elucidate the molecular mechanisms by which Brg1 influences ureterogenesis.
Main Methods:
- Conditional ablation of Brg1 in ureteric epithelium using Hoxb7-Cre mouse model.
- Analysis of gene expression (p63, Pparγ, sonic hedgehog [Shh]) and histological examination of ureter development.
Main Results:
- Brg1 is essential for ureter development, acting upstream of p63, Pparγ, and Shh.
- Brg1-dependent p63 maintains basal cell stratification, while Brg1-dependent Pparγ drives umbrella cell differentiation.
- Loss of Brg1 disrupts Shh expression, leading to impaired smooth muscle development and hydroureter.
Conclusions:
- Brg1 plays a unifying role in ureter development.
- It maintains basal cell populations, guides urothelial cell terminal differentiation, and ensures proper smooth muscle investment.
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