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Exploring sex-specific behavior at the
genetic level

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January 2018

Florida State University College of Medicine researcher Michelle Arbeitman is exploring the elaborate courtship displays of male fruit flies to better understand how one’s genetic makeup influences a range of complex behaviors.

Arbeitman has received two grants totaling $2.2 million from the National Institutes of Health. One focuses on genes and epigenetic changes that cause behavioral differences between males and females. The other looks at the nervous system and how different neuronal connections make males and females behave differently.

“The genetics of behavior is an area of research where there are still many unanswered questions, even in a relatively simple model system such as the fruit fly,” Arbeitman said. “It’s important to understand how these processes work, because defects in them will be informative about how mental health and behavioral disorders arise in humans.”

One molecular-genetic mechanism she’s exploring is how DNA modifications that change during the life of an organism — that is, epigenetic changes — occur in response to sex differences and different experiences. Example: the male fruit fly that is rejected by a female.

Scientists previously discovered that a single regulatory gene called fruitless produces male-specific proteins necessary for male reproductive behaviors in fruit flies.

“Things like the environment, sex differences, the stage of development, life experiences and nutrition contribute to differences in DNA modification,” Arbeitman said. “For example, these DNA modifications change during learning and memory formation in humans and the fruit fly. DNA modifications may also underlie adverse life events in humans, like stress and long-term drug addiction.

“What fruitless does is recruit chromatin-modifying enzymes to different regions of the genome, which establishes whether a gene is likely to be turned on. We think that fruitless both specifies the potential for behavior and the maintenance of the potential for the behavior through epigenetic modifications of DNA.”

Her team’s findings may help lay a foundation to better understand human neurological diseases. In certain mental health and behavioral disorders, various genes can be turned on or off due to epigenetic changes, causing them to switch away from their normal or healthy state.

In her second study — backed by a four-year, $1.2 million NIH grant — Arbeitman will also use the fruit fly to study sex-specific differences in neural circuit formation in the brain and how those differences drive reproductive behaviors.

Male and female fruit flies have very similar neuronal architecture, even in the neurons that specify differences in reproductive behaviors.

“The major question here is to understand how differences in males and females arise when neurons get wired together differently during development,” she said.

Arbeitman has previously identified a family of molecules that, in addition to fruitless, have important functions in male courtship behaviors.

“We’re studying a set of molecules that direct neuronal connectivity by serving as landmarks to tell one neuron to connect to another,” she said. “It’s not just connections, but also how strong those connections are. We think these differences ultimately create the vastly different behaviors seen in males and females.”