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Dissection and Culture of Mouse Embryonic Kidney
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Dicer function is required in the metanephric mesenchyme for early kidney development
Jessica Y S Chu1, Sunder Sims-Lucas, Daniel S Bushnell
1Div. of Nephrology, Dept. of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Rangos Research Center, 4401 Penn Ave., Pittsburgh, PA 15224. jacqueline.ho2@chp.edu.
American Journal of Physiology. Renal Physiology
|February 7, 2014
Summary
MicroRNAs (miRNAs) are essential for early kidney development. Ablating Dicer, which processes miRNAs, in the metanephric mesenchyme caused severe renal dysgenesis and progenitor cell death, highlighting miRNAs' crucial survival role.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are small, noncoding RNAs regulating gene expression post-transcriptionally.
- Dicer, an RNase III enzyme, is essential for miRNA maturation.
- Previous studies identified miRNA roles in midgestation nephron progenitors.
Purpose of the Study:
- To investigate the role of miRNAs in early kidney development by examining the metanephric mesenchyme.
- To understand how conditional Dicer ablation in this lineage affects kidney organogenesis.
Main Methods:
- Conditional ablation of Dicer function in the metanephric mesenchyme lineage.
- Analysis of kidney development, including ureteric bud outgrowth, mesenchyme condensation, and progenitor cell markers.
- Assessment of apoptosis and expression of proapoptotic proteins.
Main Results:
- Early loss of miRNAs led to severe renal dysgenesis despite normal initial ureteric bud and mesenchyme development.
- Nephron progenitors were initially specified but showed premature loss of Cited1, increased apoptosis, and elevated Bim expression.
- Subsequent ureteric bud branching and nephron progenitor differentiation failed in mutant kidneys.
Conclusions:
- miRNAs are critically required for early kidney organogenesis.
- miRNAs play a vital role in regulating the survival of metanephric mesenchyme and nephron progenitor cells.
- This study uncovers a previously unknown requirement for miRNAs in regulating progenitor cell fate during kidney development.
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