One of the most familiar scenes of biology is that of a sperm cell merging with an egg, creating a new organism. But cell fusion is actually rare, happening in only a handful of cell types. A far less famous example, but one that's just as important for survival, is “myoblast fusion”, when embryonic cells come together to form muscle fibers.
The top panel shows a wild-type pattern of muscle fibers in a Drosophila embryo; the bottom panel shows the complete absence of muscle fibers in embryos carrying a mutant sticks-and-stones (sns) gene.
Image: Courtesy of Dr. Susan Abmayr
Susan Abmayr is trying to uncover the genetic instructions that control myoblast fusion—how a nascent muscle cell becomes the opponens digiti minimi of the pinky finger, say, rather than the massive quadriceps. Over the past several decades, she has identified several genes in the common fruit fly, Drosophila melanogaster, that are key players in this process. Because many of these genes have counterparts in humans, this work could ultimately help researchers understand muscle repair.
"When muscles regenerate, one of the things that happen is that cells fuse with the damaged muscle," Abmayr says. "Hopefully some of the things that we figure out will be relevant for how that fusion occurs."
In a parallel line of research, Abmayr and her husband, Stowers scientist Jerry Workman, are trying to sort out precisely how genes get turned on and off in fruit flies.
The couple's first collaboration blossomed in the 1970s, when they were spending long days and nights at the same bench in Robert Roeder's laboratory at Rockefeller University in New York City. At that time, Abmayr was focused on genetic transcription—the process in which DNA turns into RNA and, eventually, protein.
She turned to flies a few years later, during a postdoctoral fellowship at Harvard University. One of her former colleagues had just discovered a gene called MyoD that could transform a dish of cultured embryonic cells into muscle. Abmayr decided to go hunting for similar genes in fruit flies—which, unlike cultured cells, can be tracked throughout development. "That got me into muscles, it got me into Drosophila, and it's what my lab has continued ever since," she says.
Most of her studies focus on muscles that line the abdominal wall of fly larvae, which help the youngsters move around for a few days before they metamorphose into adults. One of Abmayr's first major achievements came out of her lab at Penn State University in 2000, when she discovered a gene called 'sticks-and-stones', or SNS. Her team found that this gene is essential for myoblast fusion. It encodes a protein that sits on the surface of myoblasts and helps them stick to cells they will later fuse with. "That turned out to be a really important protein, and it changed the direction of research in my lab," Abmayr says.
The wild-type pattern of muscle fibers in a Drosophila embryo; red corresponds to the muscle myosin protein and highlights the muscle fibers; green marks the nuclei.
Image: Courtesy of Dr. Susan Abmayr
Since moving to Stowers in 2003, Abmayr has continued digging deeper into this complicated process. Most recently, she found that myoblast fusion isn't controlled by both cells equally, as everyone had assumed. Instead, it is asymmetric: the myoblast that is not yet part of the muscle drives the whole process. "It's not a cooperation between the two cells the way many people had thought for a very long time. Instead, unfused cells actually push into the muscle fibers," she says. "So now the question is, is this how it also works in mammals?"
Abmayr also works on gene regulation research with her husband, whose office is just down the hallway. The duo talk about lab happenings during their commute to work, but other than that, they try not to bring it home. Outside of the lab, they prefer to take trips across the world, hike, garden and do a bit of home repair. "We don't talk about transcription over dinner all that much," she says, chuckling.