Finding the Family Jewels

3 December 1998 7:00 pm

Being in the right place at the right time is vital for young cells in a developing embryo. Now biologists report in today's Nature an intriguing new clue to how immature cells find their proper places: An enzyme best known for regulating cholesterol production in humans helps the future sperm and eggs of fruit flies navigate to what will become the testes and ovaries.

In the fruit fly, precursors of sperm and eggs, called germ cells, initially develop near the tail end of the embryo. A few hours after fertilization, the future sex cells begin to head toward the nascent gonads. In order to find the genes that guide that migration, geneticist Ruth Lehmann of the Howard Hughes Medical Institute at New York University Medical School and her colleagues used chemicals to cause mutations in thousands of adult fruit flies then screened their embryonic offspring for lost or misguided germ cells. Many offspring had malformed or absent gonads. One mutant, however, which they named columbus, had perfect gonads, but its germ cells ended up scattered throughout the embryo.

When they isolated the mutated gene, the researchers found that it encodes the fly version of a well-known human enzyme called HMG-CoA reductase, which regulates the manufacture of cholesterol. Its function in flies, however, is unknown. The developing gonad tissue in flies is well-stocked with the enzyme, which seems to act like a beacon for germ cells. When the team forced regions such as the developing nervous system to express the enzyme, the germ cells journeyed there rather than to the gonads.

How the enzyme attracts germ cells is still a mystery. The scientists have ruled out a role for cholesterol, because flies don't make the molecule. But other lipids are known to guide cell migrations in human brain development, and geneticist Ken Howard of University College London suspects HMG-CoA reductase might help produce a similar lipid molecule or modify a protein that attracts the germ cells. The enzyme "is doing something important to help these cells find their way," he says, but "what that thing is is anyone's guess."

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