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 doesn’t 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 Feb. 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, MCG’s 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. Mei’s 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 it’s unknown why neurons die in these diseases.
“We believe there is a retrograde signal downstream of beta-catenin or regulated by beta- catenin,” says Dr. Mei. “If you don’t have beta-catenin in the muscle, that signal may be missing and motor neurons are not happy.”
To find out what that signal is, his lab is 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,” says Dr. Mei.
Beta-catenin is a protein with many roles, including helping cells stick together, and regulating gene expression in the Wnt pathway, which is essential for development. Dr. Mei’s previous work has shown that at least in a Petri dish, when a signaling component of the Wnt pathway, called disheveled, is disturbed in muscle cells, it causes problems with their co-cultured neurons.
In the early 1900s, German-born Scientist Viktor Hamburger provided some of the first evidence of the importance of retrograde communication in proper development of motor neurons: when he removed the budding limbs of chick embryos, motor neurons decreased in number.
“ … (T)he use of transgenic animals has established the importance of muscle ß-catenin in (neuromuscular junction) formation in vivo,” write Drs. Amy K.Y. Fu, Zelda Cheung and Nancy Y. Ip, of Hong Kong University of Science and Technology in an accompanying News and Views. “These findings also underscore the emerging role of Wnt signaling proteins in the regulation of synapse development. The identification of muscle ß-catenin-dependent signals for motoneurons may also contribute to our understanding of neuromuscular disorders, including muscular dystrophy and amyotrophic lateral sclerosis.”
Toni Baker | EurekAlert!
Carefully crafted light pulses control neuron activity
20.11.2017 | University of Illinois at Urbana-Champaign
Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
20.11.2017 | Life Sciences
20.11.2017 | Trade Fair News
20.11.2017 | Earth Sciences