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2-way cell talk provides clues about neuromuscular disease
Date:2/17/2008

Its a scientific given that neurons tell other cells what to do, but new evidence suggests that, like with any good relationship, these target cells also have much to contribute, scientists say.

In an animal model, Medical College of Georgia researchers have shown that if a muscle cell fails to produce the protein beta-catenin, its neuron doesnt develop or function properly.

Their finding provides some of the first proof that in vertebrates such as man, this retrograde communication from the target cell back to the neuron is essential, says Dr. Lin Mei, corresponding author on research published online Sept. 17 in Nature Neuroscience.

Previously, we thought signals flow mainly from neuron to muscle. This shows they can be produced from muscle, says Dr. Mei, MCGs chief of developmental neurobiology and Georgia Research Alliance Eminent Scholar in Neuroscience. This is some of the first clear genetic evidence that when you disturb something in the muscle, you have a nerve problem.

Dr. Meis research team knocked out beta-catenin in the muscle cells of a developing mouse. As a result, nerve terminals, which reach out to target cells, were misaligned. Release of neurotransmitters, which enable cell talk, from the tiny vesicles inside nerve terminals was impaired. Mice died prematurely. Two-way communication is absolutely essential, he says. Interestingly when the researchers knocked beta-catenin out of neurons instead, neurons developed and functioned normally.

Theoretically the finding is very important in that it supports the retrograde hypothesis, Dr. Mei says. 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, noting that its unknown why neurons die in these diseases.

We believe there is a retrograde signal downstream of beta-catenin or regulated by
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert  

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2-way cell talk provides clues about neuromuscular disease
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