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s, and they look very different and behave very different than they did previously. It happens more rapidly in insects, but they go through a transformation in very much the same way."

DHR4 stands for Drosophila (the genus name for fruit flies) hormone receptor 4. The DHR4 gene carries inherited instructions for cells to make the DHR4 protein, which is a "nuclear hormone receptor." Hormones like estrogen and testosterone attach to these receptors, which in turn attach to genes in cell nuclei to switch the genes on or off. Nuclear hormone receptors are found in all animals, including flies and humans, and are linked to maturation.

"So concluding that nuclear receptors are critical for the timing of onset of maturation [in flies] is a logical conclusion we could extend to humans," Thummel says.

Thummel and colleagues raised fruit flies in vials containing a gelatinous food made of agar, cornmeal, molasses and yeast. The scientists disabled the DHR4 gene using two methods: conventional "knockout" technology and a newer method in which the gene was "silenced."

By showing what happened when the gene was disabled, the researchers determined the normal gene has two key functions:

* DHR4 determines when metamorphosis should begin, when the fly should begin changing from juvenile to adult. If the gene was crippled, fly larvae started metamorphosis too soon, and became prepupae that were lighter and shorter than normal.

* The gene also is needed for the early stages of metamorphosis to proceed; it plays a role in turning on and off other genes that control metamorphosis in response to a steroid hormone named ecdysone, which is emitted by a gland as the larval stages end. When the gene was disabled, the fly larvae started metamorphosis but died within 12 hours. In some, their heads failed to emerge from their bodies.

"How does an animal know when it is ready to mature ?what determines that time?" Thummel asks. "Th
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Source:MWG Biotech AG


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