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DNA Microarrays Point to Genes Causing Hirschsprung Disease

By Biotechdaily staff writers
Posted on 27 Aug 2003
A recent study has found that Hirschsprung disease, a common genetic disorder occurring about one in every 5,000 births, is caused by defects in neural crest stem cell function that prevent the stem cells from differentiating into the nerves that control the lower intestine.

Investigators at the Howard Hughes Medical Institute (Chevy Chase, MD, USA) and the University of Michigan (Ann Arbor, USA) employed DNA microarrays to conduct a global comparison of genes expressed in whole mouse fetuses with those genes expressed only in the fetal gut neural crest stem cells. More...
They found that the 10 genes that were most highly expressed in the gut neural crest stem cells relative to the whole fetus included four that had already been linked to Hirschsprung disease in humans.

One of these genes, the glial cell line–derived neurotrophic factor (GDNF) receptor Ret, was confirmed to be necessary for neural crest stem cell migration in the gut. GDNF promoted the migration of neural crest stem cells in culture but did not affect their survival or proliferation.

"Until this work, what was missing was whether these molecular pathways act within neural crest stem cells to promote migration,” explained senior author Dr. Sean Morrison, assistant professor of cell and developmental biology at the University of Michigan. "Our finding that these pathways are all expressed in neural crest stem cells and that they regulate the function of the cells, provides a cellular locus for people to study directly how those pathways interact. We think that this represents a powerful combination for getting important insights into the causes of other types of birth defects or other types of diseases.”





Related Links:
Howard Hughes Medical Institute
University of Michigan

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