Researchers at the University of Buffalo’s Hunter James Kelly Research Institute (HJKRI) discovered that the cells that form myelin in the nervous system respond to mechanical stimulation by activating molecules from a specific pathway, which are transferred to the nucleus, triggering myelination.
The findings, which may be key to developing new therapies for myelin diseases such as multiple sclerosis (MS), were published in the journal Nature Neuroscience, in the study “YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells.“
“There were hints in previous studies that mechanical properties of tissues could influence the behavior of myelin-forming cells,” M. Laura Feltri, MD, the study’s senior author, a professor of biochemistry and neurology in the Jacobs School of Medicine and Biomedical Sciences at Buffalo and a researcher at HJKRI, said in a press release. “Our work proves for the first time, in vivo, that this is indeed the case. We have demonstrated that mechanical information is necessary for myelination to occur.”
Mechanical signaling is already accepted as a major factor in the injury and repair of muscles and bones. Putting weight on a broken bone is known to generate a mechanical force that improves the formation of new bone cells. “Now we know that a similar phenomenon is occurring with myelin cells,” she said.
The study also found that Yap and Taz, two proteins of the Hippo pathway known to be crucial for mechanical signal transduction by moving into the nucleus and regulating gene expression upon a mechanical stimuli, were involved in myelin formation. When mice were genetically engineered to lack these proteins, they showed symptoms of severe peripheral neuropathy, including atrophy, weakness, and tremor.
Such findings may pave the way for the development of new therapies for myelin-related disorders.
“Most medical treatments are based on altering chemical signals,” Dr. Feltri said. “This work says there is another level of control in myelin diseases that we can learn from and possibly exploit in the future. Potentially, in the future, we will be able to exploit a tissue’s mechanical properties, including the density, tension or elasticity of some part of the brain or peripheral nerves.”