Undergrad’s passion spurred by mice muscle regeneration research
By Samantha Kummerer | Bond LSC
Uncertainty and curiosity led Rebecca Craigg to work in a lab.
As a first-generation college student with an interest in science but no idea what undergraduate research entailed, her path at the University of Missouri landed her in the Bond Life Sciences Center and the lab of D Cornelison.
“I honestly thought undergraduate research meant you just followed around someone like job shadowing,” she said laughing.
Now, after almost a year of research, the junior biology major is more than familiar with what working in a lab entails.
Craigg started working in Cornelison’s lab as an effort to figure out what kind of science she might be interested in. It was while she waited for her genetically altered mice to grow up when she found something that really sparked her interest.
Rather than spend her time cleaning lab dishes, Craigg began assisting a graduate student on a project studying the role of EphA7 in mice. EphA7 is a receptor on cells that helps mediate important events within the body. Receptors create a change in the body after receiving a signal from outside the cell. The exact hows and whys behind the EphA7 are still relatively unknown.
To unravel EphA7 the team began by breeding genetically altered mice with the gene switched off. Next, specific muscles were isolated, dissected, and preserved once the mice reached different developmental time points. Researchers thinly sliced the muscle and added immunofluorescent staining to track specific elements over a period of time. They marked EphA7 with a green fluorescent and regenerating muscle fibers with red. Imaging revealed every time green came up so did red. This led researchers to understand that EphA7 is connected to how muscles rebuild.
But this isn’t the only role the receptor plays.
Work this summer also discovered the gene is involved in the development of muscles. The team found at the end of development, the mice without EphA7 did not fully recover like they would have if they were not modified. When the team looked at marking for muscle stem cells, both the mice with the receptor and the mice without it had a depleted number of satellite cells, essentially muscle stem cells, that did not recover.
Craigg explained this discovery was puzzling.
In every other case heterozygous mice, the mice with one gene coded with EphA7, were fine. The team predicts the cells and muscles realized they were not adequate so the muscle stem cells began to become muscles. This process would leave fewer stem cells at the end of development.
Fewer muscle fibers really mean the mice are lacking normal muscle strength. Craigg said one reason for this could be EphA7’s relation to motor neuron axons. Motor neurons send signals from the nervous system to muscles to tell them to move. EphA7 is present on all motor neurons. The team hypothesized that the gene may play a role in guiding the motor axon to the muscle, thus without it, muscle size would decrease.
“We kind of know way more than we did, obviously, in that it’s involved in regeneration and all these things and that if a mouse doesn’t have it they have all these decreased numbers all over the board, but we don’t know why per say,” Craigg said.
To better understand why EphA7 functions the way it does, the team will begin to examine the relationship between motor neurons and EphA7. They will also explore if the type of muscle fiber, slow-twitch versus fast twitch, make a difference.
Craigg said each new piece of knowledge about EphA7 is a step towards better understanding what causes muscle disease in humans.
While the lab faces a lot more work ahead, it doesn’t faze Craigg. For her, the possibility of more discoveries is part of the thrill.
“We kept finding out so many new things about it. I would be counting things and I’d be like, ‘Oh my god, I can’t wait to get this data back, like, I just want to know,’” she exclaimed.
Rebecca Craigg is a junior biology major working in the lab of D Cornelison at Bond LSC.