When one encounters a group of fruit flies invading their kitchen, it probably appears as if the whole group is vying¹（争夺） for a sweet treat. But a closer look would likely reveal the male flies in the group are putting up more of a fight, particularly if ripe fruit or female flies are present.

 

According to the latest studies from the fly laboratory of California Institute of Technology (Caltech) biologist David Anderson, male Drosophilae, commonly known as fruit flies, fight more than their female counterparts because they have special cells in their brains that promote fighting. These cells appear to be absent in the brains of female fruit flies. "The sex-specific cells that we identified exert their effects on fighting by releasing a particular type of neuropeptide（神经肽）, or hormone², that has also been implicated³ in aggression⁴ in mammals including mouse and rat," says Anderson, the Seymour Benzer Professor of Biology at Caltech, and corresponding author of the study. "In addition, there are some recent papers implicating⁵ increased levels of this hormone in people with personality disorders⁶ that lead to higher levels of aggression."

 

The team's findings are outlined in the January 16 version of the journal Cell.

 

At first glance, a fruit fly may seem nothing like a human being. But look much closer, at a genetic⁸ level, and you will find that many of the genes⁹ seen in these flies are also present -- and play similar roles -- in humans. However, while such conservation holds for genes involved in basic cellular¹⁰ functions and in development, whether it was also true for genes controlling complex social behaviors like aggression was far from clear.

 

"Our studies are the first, to our knowledge, to identify a gene⁷ that plays a conserved¹¹ role in aggression all the way from flies to humans," explains Anderson, who is also a Howard Hughes Medical Institute investigator¹². If that is true for one such gene, it is also is likely true for others, Anderson says. "Our study validates¹³ using fruit flies as a model to discover new genes that may also control aggression in humans."

 

The less-complex nervous system of the fruit fly makes them easier to study than people or even mice, another genetic model organism. For this particular study, the research team created a small library consisting of different fly lines; in each line, a different set of specific neurons was genetically¹⁴ labeled and could be artificially activated¹⁵, with each neuron type secreting¹⁶ a different neuropeptide. Forty such lines were tested for their ability to increase aggression when their labeled neurons were activated. The one that produced the most dramatic increase in aggression had neurons expressing a particular neuropeptide called tachykinin, or Tk.

 

Next, Anderson and his colleagues used a set of genetic tools to identify exactly which neurons were responsible for the effect on aggression and to see if the gene that encodes for Tk also controls aggressive behavior by acting¹⁷ in that cell.

 

"We had to winnow¹⁸ away the different cells to find exactly which ones were involved in aggression -- that's how we discovered that within this line, there was a male-specific set of neurons that was responsible for increased aggressive behavior," explains Kenta Asahina, a postdoctoral scholar in Anderson's lab and lead author of the study. Male-specific neurons controlling courtship behavior had previously¹⁹ been identified in flies, but this was the first time a male-specific neuron was found that specifically controls aggression. Having identified that neuron, the team was then able to modify its gene expression. Says Asahina, "We found that if you overproduce the gene in that cell and then stimulate²⁰ the cell, you get an even stronger effect to promote aggression than if you stimulate the cell without overproducing the gene."

 

In fact, combining cell activation²¹ and the overproduction of the neuropeptide, which is released when the cell is activated, caused the flies to attack targets they normally would not. For example, when the researchers eliminated cues that normally promote aggression in a target fly -- such as pheromones -- the flies containing the hyperactivated "aggression" neurons attacked those targets despite the absence of the cues.

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