U.S. Department of Health and Human Services

New Insights into Kidney Formation

New research indicates that the protein called Dicer plays an important role in kidney development by regulating micro-ribonucleic acid (miRNAs). The discovery of molecules known as miRNA has challenged the prevailing scientific thinking about the role of RNA in gene expression, the process by which information stored within DNA is decoded into messenger RNA (mRNA) which in turn is translated into a protein. Different genes produce different mRNAs, which code for different proteins. Both mRNA and miRNA are made up of a string of nucleic acids; however, miRNA is much shorter than mRNA. miRNAs can interact with mRNA to block the ability of mRNA to be translated into protein, thereby adding another level where gene expression can be regulated. Mammalian genomes contain a large and diverse family of miRNAs. It is now believed that miRNAs might affect one-third of all human gene expression. 

The protein Dicer plays a key role in processing miRNA from its initial long pre-miRNA form to its shortened, mature form. Scientists sought to determine the role, if any, of Dicer and miRNAs in regulating kidney development. To investigate Dicer’s potential role, mice were genetically altered to remove Dicer function from cells that form the nephron and ureteric bud-derived collecting duct system—two compartments of the mammalian kidney. Kidneys were removed prior to or shortly after birth and evaluated for developmental abnormalities. Lack of Dicer function in cells destined to become part of the nephron led to increased cell death, incomplete nephron formation, and smaller kidneys. Removal of Dicer function from the ureteric bud resulted in the development of kidney cysts (sacks of fluid that replace healthy tissue). In addition, Dicer removal disrupted normal structural features of the ureteric bud. 
 
This study provides evidence that Dicer, and presumably the miRNAs processed by Dicer, have distinct and critical regulatory roles within different components of the developing kidney. Further investigation of the role of miRNAs might shed new light into understanding how the number of functioning nephrons in the kidney is determined and the underlying causes and development of cystic kidney diseases.

Nagalakshmi VK, Ren Q, Pugh MM, et al. Dicer regulates the development of nephrogenic ​and ureteric compartments in the mammalian kidney. Kidney Int 79: 317-330, 2011.