Why can zebrafish regenerate damaged gut nerves while humans largely cannot?
Michigan State University researchers have developed a powerful new research tool that allows them to remove gut neurons in zebrafish and watch them regenerate in real time, helping scientists investigate one of regenerative biology’s biggest questions.
The research focuses on the enteric nervous system, often called the body‘s “second brain.“ This vast network of neurons is embedded throughout the digestive tract and contains roughly as many neurons as the spinal cord. It controls digestion, nutrient absorption and the movement of food through the gut while remaining in constant communication with the brain.
Although humans and other mammals have only a limited ability to replace damaged gut neurons, zebrafish can rebuild those neural networks within days.
“We knew zebrafish could regenerate nervous system tissue,” said Julia Ganz, associate professor in MSU’s College of Natural Science. “But we didn’t know exactly how regeneration happens in the gut nervous system.”
Using the new system, Ganz and her team selectively removed gut neurons in larval zebrafish and watched new neurons regenerate and reconnect with existing neural networks in about nine days.
“The neurons don’t just come back,” Ganz said. “They integrate into the existing nervous system and appear to resume the jobs they were performing before.”
The findings showed that the regenerated neurons not only replaced lost cells but also restored the neural connections needed for normal gut function.
More importantly, the new system gives researchers a controlled way to trigger gut nerve regeneration and investigate the cells, genes and molecular signals that make regeneration possible.
“We’re already looking at what signals play a role in this regenerative response and what cell populations are needed,” Ganz said during an interview. “Once we have a better understanding of how zebrafish accomplish this, the next step is to compare that process with mammals and figure out what’s different.”
The long-term goal is to understand why regeneration occurs so readily in zebrafish but is far more limited in mammals — knowledge that could eventually help researchers develop ways to repair damaged nerves instead of simply treating the symptoms caused by nerve loss.
“Right now, many treatments focus on managing symptoms or surgically removing damaged portions of the digestive tract,” Ganz said. “If we can understand how regeneration works in zebrafish, it may eventually help us develop ways to repair the nervous system itself.”
The findings could eventually have implications for digestive disorders, inflammatory diseases, congenital conditions involving the loss of gut nerves and other diseases that affect the enteric nervous system.
The research was published in Stem Cell Reports.
