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How to build a kidney
  
By Bijal P. Trivedi

Researchers are learning how the body builds a kidney by discovering which genes are active during specific stages of development. One third of all chronic kidney diseases is due to problems during kidney development.

Robert Stuart, of the University of California at San Diego, and colleagues used gene chips, or DNA microarrays as they are also known, to analyze the activity of 8,740 rat genes and identify the ones involved in the development and maturation of the kidney. The team examined gene activity at seven stages of development: 13, 15, 17, and 19 day-old rat embryos, newborns, one-week-old rats and adults. Of the genes represented on the chip, 873 showed significant activity during kidney formation. The study is reported in the current issue of Proceedings of the National Academy of Sciences.

The genes fell into five distinct groups based on function. The earliest stage of kidney development seems to be governed by genes that play roles in protein and RNA production and modification, and the replication of DNA. The researchers suggest that, during this period, the kidney's job is simply to grow—hence the genes that are active during this early stage are dedicated to increasing the number of cells.

Many genes that characterize the next stage of embryonic development produce structural proteins that reshape the architecture of the cell's local environment and create scaffolding that defines the shape of the kidney.

The third group of genes, which is activated around the time of birth, is the most puzzling to Stuart's team. These genes, which produce retrotransposon RNA, are from viruses that incorporated their genome into a rat chromosome millions of years ago. Why these viral genes are activated during birth, and what they do, is not known. The authors speculate that these viral genes may be part of a stress response that is triggered at birth.

The fourth group of genes that becomes active after birth produces proteins that are involved with energy production. This burst in the production of energy-producing proteins anticipates the future needs of the kidney, whose job it is to reabsorb water and nutrients and secrete wastes. Transporting water, salt, toxins, and urea in and out of the cell requires a considerable amount of energy. The fifth category of genes produces transporter proteins that shuttle these substances in and out of the cell.

Stuart's study is the first to examine gene expression as the kidney develops from embryonic stages to its final role as the body's filtration system.

"The ultimate goal of kidney research is to one day grow replacement kidneys in the lab," Stuart was quoted as saying. "Until then, we are trying to understand all that is going on in the kidney as it develops." Understanding which genes contribute to each stage may help researchers to develop therapies.

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Stuart, R.O. et al. Changes in global gene expression patterns during development and maturation of the rat kidney. Proc Natl Acad Sci USA 98, 5649-5654 (May 8, 2001).
 

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