Key Gene Controlling Kidney Development Found
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A gene called Six2 plays a critical role in the development of the kidney by keeping a population of "parent" stem cells constantly available to produce the differentiated cells that give rise to specialized parts of the organ, according to investigators at St. Jude Children's Research Hospital.
The kidney stem cells, called mesenchymal blastemal cells, are the source of cells triggered by chemical signals to differentiate into nephrons - the structures in the kidney that cleanse the blood of waste.
The St. Jude team showed that Six2 works by preventing some of the precursor cells from responding to these signals.
That ensures that there will be a continual source of undifferentiated stem cells available to maintain the growth of the kidney.
"Our work shows that Six2 is critical to preventing the developing kidney from running out of stem cells and collapsing into a mass of underdeveloped tissue," said Guillermo Oliver, Ph.D., a member of the St. Jude Department of Genetics and Tumor Cell Biology.
Oliver is senior author of a report on this finding that appears in the online issue of The EMBO Journal.
"Our discovery of the role of Six2 in the developing kidney suggests that a similar mechanism exists in other developing organs," noted Michelle Self, the doctoral student in Oliver's laboratory who did most of the work on this project.
The researchers also found that Six2 works by suppressing a cascade of genetic interactions normally triggered by a gene called Wnt4, which usually drives the normal development of kidneys.
