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Key
gene controlling kidney development found
St. Jude researchers show that the Six2 gene prevents
kidney stem cells from differentiating so they continue to
produce specialized cells that help to build the organ
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.
Differentiation is the process by which a progenitor (unspecialized)
cell develops characteristics specific to its job in the body.
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 nephrons
later become attached to ducts--tubes that collect the filtered
blood as urine and direct it to the bladder. The St. Jude
team showed that Six2 works by preventing some of the precursor
cells from responding to these signals. This ensures 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 Genetics and Tumor Cell Biology Department. Oliver
is senior author of a report on this finding that appears
in the online issue of The EMBO Journal.
"Our discovery of Six2's
role in the developing kidney suggests that a similar mechanism
exists in other developing organs," said Michelle Self,
the doctoral student in Oliver's laboratory who did most of
the work on this project.
The St. Jude team showed that the kidneys in developing mice
lacking the Six2 gene were remarkably smaller than normal
mice and were non-functional at birth. In addition, they produced
an abnormal excess in the number of nephrons that in turn
produced a useless mass of tissue. Furthermore, the remaining
precursor cells underwent apoptosis (cell suicide), further
depleting the population of stem cells that could give rise
to differentiated cells needed to form the kidney.
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.
Contact:
Bonnie Kourvelas
bonnie.kourvelas@stjude.org
901-495-4815
St. Jude Children's Research Hospital
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