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!
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences