Fruit fly cells don’t all know what sex they are.

Only some cells in a fly’s leg express the doublesex gene (red).

Scientists who spend hours each day poring over fruit fly biology can easily distinguish a male fruit fly from a female under the microscope. But place an individual cell from a fly under the scope and ask whether it is male or female, and you’ll surely stump them.

HHMI scientists have now found that many cells in male and female fruit flies not only look the same, they are more identical at a molecular level than was previously thought.

“It’s been a widely accepted paradigm that all cells know their sex,” says Bruce Baker, a group leader at HHMI’s Janelia Farm Research Campus and an author of the new study. Researchers believed that all somatic cells in a fruit fly expressed doublesex, a gene known to control sex determination in flies. Females and males differed as a consequence of the expression of sex-specific Doublesex proteins.

“This was a good model. It worked fine for explaining what we knew. But it had never been rigorously tested,” says Baker. Now it has.

Baker and his colleagues genetically engineered fruit flies so that when a cell made protein from the doublesex gene, the cell lit up. The researchers then tracked the development of these fruit flies from embryos onward, watching which cells lit up.

They observed that, beginning 12 hours after fertilization, only some cells in the embryos express doublesex. Expression of the gene varies among cells and tissues throughout development. By the time the fly is an adult, only a portion of the fly’s tissues have doublesex turned on—including all regions of the fly with obvious sex differences, like the genitalia. However, many cells, they found, turn off doublesex permanently. Thus, in fruit flies both males and females are sexual mosaics, in that some cells know their sex, whereas other cells do not. The research was published on May 4, 2010, in PLoS Biology.

Since doublesex is a conserved sex determination gene in many animal species, including humans, Baker and his coauthors suggest their results may foreshadow similar findings in other animal species.

Photo: Baker Lab