Nav: Home

Signposts to the muscles

March 01, 2016

In both humans and animals, voluntary movement is the result of a complex and precisely-coordinated interplay of nerves, muscles and bones. How does this 'neuromuscular unit' develop during early embryonic development, and which genes are involved? "This is the question we asked ourselves, particularly in the case of certain patients born with broken bones who, even as newborns, were neither able to move properly nor breathe unaided," explains Dr. Ellen Knierim, a researcher at Charité's NeuroCure Clinical Research Center and the study's first author. "Our attempts to determine the causes behind the disorder were greatly aided by gene sequencing technology and biocomputational analysis," adds Dr. Knierim.

Using these techniques, the researchers were able to discover mutations in the ASC-1 protein complex of affected patients. They found that ASC-1 controls numerous factors responsible for guiding the development of peripheral motor neurons, as they grow from their places of origin inside the spinal cord to their respective target muscles. At the same time, researchers led by Prof. Hiromi Hirata from Japan's Aoyama Gakuin University conducted research to establish the function of the ASC-1 complex in zebrafish, where its deliberate elimination leads to paralysis. Using the fish's virtually transparent larvae, Hirata was able to show that nerve cells emanating from the spinal cord were unable to find their target muscles.

"As a 'transcription factor', the ASC-1 complex controls the activity of nerve growth factors by switching them on and off as required," explains Prof. Markus Schuelke, who heads the research group at Charité. "In a manner reminiscent of crash barriers ensuring a vehicle does not leave the road, these factors effectively keep the growing nerve cells on the right track, ensuring they safely reach their intended destinations." Additional experiments conducted by the group showed that the ASC-1 complex works in cooperation with a specific protein (CSRP1). The protein itself has been known to researchers for some time as a result of research on zebrafish, where it plays an important role in the healing process following damage to the spinal cord. In contrast to humans, zebrafish are able to regenerate their spinal cord, even if it has been completely severed. It would appear that the CSRP1 protein plays an important role in this process.

Prof. Schuelke emphasizes: "Our results are a good example of how the study of rare genetic diseases can provide insights into general disease mechanisms, which may also play a role in other conditions, such as paraplegia, and which may give rise to the development of regenerative therapies."
Knierim E., Hirata H., Wolf N.I., Morales-Gonzalez S, Schottmann G., Tanaka Y, Rudnik-Schöneborn S., Orgeur M., Zerres K., Vogt S., van Riesen A., Gill E., Seifert F., Zwirner A., Kirschner J., Goebel HH., Hübner C., Stricker S., Meierhofer D, Stenzel W., Schuelke M. Mutations in Subunits of the Activating Signal Cointegrator 1 Complex Are Associated with Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures. The American Journal of Human Genetics. Available online 25 February 2016, ISSN 00029297.


Prof. Dr. med. Markus Schuelke
Department of Pediatrics, Division of Neurology
Campus Virchow Klinikum
Tel: +49 30 450 566 468 / -112


Department of Pediatrics, Division of Neurology

Neurocure Cluster of Excellence

Charité - Universitätsmedizin Berlin

Related Spinal Cord Articles:

Stem cells can help repair spinal cord after injury
Spinal cord injury often leads to permanent functional impairment. In a new study published in the journal Science researchers at Karolinska Institutet in Sweden show that it is possible to stimulate stem cells in the mouse spinal cord to form large amounts of new oligodendrocytes, cells that are essential to the ability of neurons to transmit signals, and thus to help repair the spinal cord after injury.
Improving treatment of spinal cord injuries
A group led by UC Riverside bioengineering professor Victor G.
Spinal cord gives bio-bots walking rhythm
Miniature biological robots are making greater strides than ever, thanks to the spinal cord directing their steps.
Co-delivery of IL-10 and NT-3 to enhance spinal cord injury repair
Spinal cord injury (SCI) creates a complex microenvironment that is not conducive to repair; growth factors are in short supply, whereas factors that inhibit regeneration are plentiful.
Locomotor engine in the spinal cord revealed
Researchers at Karolinska Institutet in Sweden have revealed a new principle of organization which explains how locomotion is coordinated in vertebrates akin to an engine with three gears.
Neurological signals from the spinal cord surprise scientists
With a study of the network between nerve and muscle cells in turtles, researchers from the University of Copenhagen have gained new insight into the way in which movements are generated and maintained.
An 'EpiPen' for spinal cord injuries
An injection of nanoparticles can prevent the body's immune system from overreacting to trauma, potentially preventing some spinal cord injuries from resulting in paralysis.
From spinal cord injury to recovery
Spinal cord injury disconnects communication between the brain and the spinal cord, disrupting control over part of the body.
Transplanting adult spinal cord tissues: A new strategy of repair spinal cord injury
Spinal cord injury repair is one of the most challenging medical problems, and no effective therapeutic methods has been developed.
Gene medication to help treat spinal cord injuries
The two-gene medication has been proven to recover motor functions in rats.
More Spinal Cord News and Spinal Cord Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at     You can read The Transition Integrity Project's report here.