Most general biology courses, when discussing neuronal cell development, will highlight the importance of myelination for nerve impulse conduction. Often, Schwann cells are mentioned in these biological conversations but regularly relegated to not much more than an afterthought. Well now, a team of investigators from the Vollum Institute at Oregon Health & Science University (OHSU) are looking to change how people view Schwann cells, as they just released new data showing that this cell type is much more prolific in generating a protective sheath covering nerve fibers than previously believed—potentially leading to new therapies that could heal nervous system disorders or injuries.
“This totally overturns the textbook definition of the way Schwann cells work,” said senior author Kelly Monk, PhD, professor and co-director of the Vollum Institute at OHSU.
The revelation about Schwann cells raises the possibility of new avenues to treat nerve injuries and various forms of neuropathy. Further research could prove useful in promoting myelin repair in central nervous system disorders such as multiple sclerosis, where damage to myelin slows or blocks electric signals from the brain. Findings from the new study were published recently in Nature Communications through an article titled “Myelinating Schwann cells ensheath multiple axons in the absence of E3 ligase component Fbxw7.”
The research team made the discovery after conducting a genetic screen in zebrafish in the Monk laboratory. They discovered some fish had more myelin than expected, and those fish carried a mutation in a gene called fbxw7. When they knocked out the gene in genetically modified mice, they discovered an unexpected characteristic: individual Schwann cells began spreading myelin across many axons.
“We find that loss of Fbxw7, an E3 ubiquitin ligase component, enhances the myelinating potential of SCs,” the authors wrote. “Fbxw7 mutant SCs make thicker myelin sheaths and sometimes appear to myelinate multiple axons in a fashion reminiscent of oligodendrocytes. Several Fbxw7 mutant phenotypes are due to dysregulation of mTOR; however, the remarkable ability of mutant SCs to ensheathe multiple axons is independent of mTOR signaling. This indicates distinct roles for Fbxw7 in SC biology including modes of axon interactions previously thought to fundamentally distinguish myelinating SCs from oligodendrocytes.”
“It highlights a very plastic potential for these cells,” Monk added.
In discovering how Schwann cells generate myelin at the molecular level, the discovery may lead to new gene-therapy techniques to repair damaged myelin in peripheral nervous system disorders such as Charcot-Marie-Tooth disease, a painful inherited form of neuropathy that affects 1 in 2,500 people in the United States.
Both Schwann cells and oligodendrocytes arose at the same point in evolutionary history, with the appearance of jaws in the vertebrate lineage. Invertebrates lack myelin, and some, like the modern squid, use thick axons to quickly transmit signals between neurons.
Instead, vertebrate axons evolved myelin to protect axons and speed up the signal transmission. To create myelin, Schwann cells evolved to produce it around a single axon in the peripheral nervous system. Oligodendrocytes, in turn, generated myelin along multiple axons within the more confined environment of the brain and spine—the central nervous system.
“The real estate is fundamentally different in the central nervous system than in the peripheral nervous system,” Monk noted.
Monk theorizes that Schwann cells evolved a mechanism to repair damaged myelin on a cell by cell basis since it would have been common for injuries to occur without necessarily killing the entire organism. Those traits would have been passed down and strengthened through generations of evolution.
By contrast, remyelination in the central nervous system tended to be an evolutionary dead end since few would have survived a severe whack to the brain or spine.
“There’s no selective pressure in repairing myelin damage in the central nervous system because you’re probably going to die,” Monk said.
However, the discovery published today suggests a new opportunity to heal the brain and spine.
“Targeting the fbxw7 gene—or downstream pathway molecules—could be a powerful way to promote myelin repair in the central nervous system,” Monk concluded.