Scientists at the Medical College of Georgia have discovered that neurons stop functioning properly in mice when a muscle cell fails to produce the protein beta-catenin.
Dr. Lin Mei, chief of developmental neurobiology and Georgia Research Alliance Eminent Scholar in Neuroscience, says that this is the first proof that this retrograde communication—from the target cell back to the neuron—is essential in vertebrates such as man
"Previously, we thought signals flow mainly from neuron to muscle. This shows they can be produced from muscle. This is some of the first clear genetic evidence that when you disturb something in the muscle, you have a nerve problem," Nature Neuroscience quoted Dr. Mei as saying.
The researcher revealed that nerve terminals, which reach out to target cells, were misaligned when his team knocked out beta-catenin in the muscle cells of a developing mouse.
This impaired the release of neurotransmitters, which enable cell talk, from the tiny vesicles inside nerve terminals, and in turn caused the mice to die prematurely.
"Two-way communication is absolutely essential," Dr. Mei said.
Interestingly, when beta-catenin was knocked out of neurons instead, the neurons kept developing and functioning normally.
"Theoretically the finding is very important in that it supports the retrograde hypothesis. Practically it is also important because problems with motor neuron survival and differentiation cause many neuromuscular diseases, such as muscular dystrophy and ALS, where motor neurons need to survive," Dr. Mei said.
The researcher, however, noted that it was unknown why neurons die in such diseases.
"We believe there is a retrograde signal downstream of beta-catenin or regulated by beta- catenin. If you don't have beta-catenin in the muscle, that signal may be missing and motor neurons are not happy," said Dr. Mei.
With a view to discerning what that signal is, Dr. Mei and his colleagues are comparing genetic expression in the beta-catenin knockout mouse to that of a normal mouse to see which genes are up or down-regulated.
"Those genes may be targeted by beta-catenin and may serve as this retrograde signal. If we can identify that, I can retire," said Dr. Mei.