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Fruit fly cells reveal Hedgehog's secrets

A Johns Hopkins-led research team has successfully used a technique to rapidly find fruit fly genes involved in a cell signaling pathway called Hedgehog, which is critical to proper embryo development and a key trigger in some cancers, including the deadly childhood brain cancer medulloblastoma.

By using the technique, called RNA interference, to "knock down" the messages of specific genes in fruit fly cells, researchers from Johns Hopkins and the National Institutes of Health screened 43 percent of the fruit fly's genes and found four new players involved in passing along Hedgehog's signal.

Reporting in the March 28 issue of Science, the scientists also suggest that the human counterparts of the fruit fly genes may be involved in birth defects and cancers characteristic of abnormal Hedgehog activity.

"Thanks to the human genome draft, we can make fairly direct connections between what we find in fruit flies and human disease," says Phil Beachy, Ph.D., a Howard Hughes Medical Institute investigator and a professor of molecular biology and genetics in Johns Hopkins' Institute for Basic Biomedical Sciences. "Our evidence suggests that human versions of these genes may be involved in disease, acting through the Hedgehog pathway."

In developing embryos of many organisms, including fruit flies, mice and humans, the Hedgehog signal ensures appropriate patterns of key proteins and cell types. Without the signal, these early developmental steps are disrupted, and severe -- usually fatal -- birth defects result. In some cancers, unnecessary activity of Hedgehog causes excessive cell growth. Understanding Hedgehog's signal one day may help prevent or correct these situations, say the researchers.

The Hedgehog pathway starts with a protein by the same name and ends with another protein that directly regulates the activity of a host of genes. A few key intermediate player
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
28-Mar-2003


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