February 19, 2008

Scientists Find Nerve-Muscle Signals Go Both Ways

Researchers in the laboratory of MDA-supported Lin Mei at the Medical College of Georgia in Augusta have found that muscle fibers do more than passively receive signals from nerve fibers that tell them to contract or relax.

Instead, say Mei and colleagues, who published their findings online today in Nature Neuroscience, “backwards” (retrograde) signals coming from muscle fibers to nerve fibers profoundly influence nerve-fiber location and function.

When the investigators bred mice lacking a protein called beta-catenin in their muscles, they saw that branches of the phrenic nerves, which go to the respiratory diaphragm, were mislocated in the diaphragm muscle and that signal transmission was reduced.

However, when beta-catenin was depleted only in nerve cells in the mice, they didn’t have this type of neurological problem.

“These observations demonstrate that muscle beta-catenin is a key ingredient for neuromuscular junction formation,” Mei said, referring to places where nerve and muscle fibers meet. The findings also showed that beta-catenin may control other proteins necessary to nerve-cell health, she added.

“Muscles are known to produce elusive nutritional factors for nerve-cell survival and development,” Mei said. “And these findings could provide leads to their identification.”

They could also have implications for a variety of neuromuscular diseases, including amyotrophic lateral sclerosis (ALS), the investigators note. In the vast majority of cases of this paralyzing and fatal disease, nerve cells that control muscle fibers die from unknown causes, some of which probably have their origins outside the ill-fated nerve cells themselves.

In an accompanying editorial, researchers from Hong Kong University of Science and Technology describe the findings’ significance as “several-fold.” They say these experiments will help scientists understand more about how neuromuscular junctions develop and may add to current understanding of neuromuscular disorders, including ALS and muscular dystrophy.