Muscle Cells Trigger Synapse Formation

Applied Genetics News,  May, 2001  

• E-mail
• Print
• Link

Investigators from the Salk Institute (10010 N. Torrey Pines Rd., La Jolla, CA 92037-1099; Tel: 619/453-4100) have examined the clustering of neurotransmitters, an indicator of synapse formation, between nerve and muscle in growing mouse embryos.

"We found that the formation of neuromuscular synapses is triggered by cues in muscle cells," says Kuo-Fen Lee, senior author of the study, which appears in the April 25 issue of Nature. "This finding overturns essentially 30 years of thinking and has implications for attempts to reconstitute a functional nervous system in cases like spinal cord injury."

When the Salk team examined 14-day-old embryos, they found that nerves did not appose receptor clusters. "That was the first clue that perhaps the initiation was nerve-independent," notes Lee. "But we couldn't rule out possibilities such as messages from nerve cells traveling further than we'd thought they could."

The group then genetically manipulated mice to create mutants that do not grow a phrenic nerve, which normally innervates the diaphragm muscle that is essential in controlling breathing. When embryonic diaphragm muscle was examined, receptor clustering in the muscle was normal.

The receptor clustering occurs along the midband of the muscle, which is where contraction will take place in the fully formed muscle. Lee and his colleagues think it is possible that by beginning to form synapses along the midband, the muscle attracts growing nerve cells to the appropriate location to form connections.

Though it is known that the nerve releases factors at later times that nourish the synapse, Lee's data suggest that the muscle determines the initial placement. "Therefore," says Lee, "if you're working on nerve regeneration in cases like spinal cord repair, it may not be enough to grow new nerves. You may have to look toward the muscle for help in establishing the proper connections to restore full function."

COPYRIGHT 2001 Business Communications Company, Inc.
COPYRIGHT 2001 Gale Group