A gene that helps regulate how well nerves of the central nervous system (lat. systematis nervosi centralis) are insulated has been identified by the scientists at Washington University School of Medicine in St. Louis (WUSTL). Healthy insulation is vital for the speedy propagation of nerve cell signals. The finding, in zebrafish and mice, may have implications for human diseases like multiple sclerosis, in which this insulation is lost. Nerve cells send electrical signals along lengthy projections called axons. These signals travel much faster when the axon is wrapped in myelin, an insulating layer of fats and proteins. In the central nervous system, the cells responsible for insulating axons are called oligodendrocytes.

The research focused on a gene called Gpr56, which manufactures a protein of the same name. Previous work indicated that this gene likely was involved in central nervous system development, but its specific roles were unclear. In the new study, the researchers found that when the protein Gpr56 is disabled, there are too few oligodendrocytes to provide insulation for all of the axons. Still, the axons looked normal. And in the relatively few axons that were insulated, the myelin also looked normal. But the researchers observed many axons that were simply bare, not wrapped in any myelin at all.

Without Gpr56, the cells responsible for applying the insulation failed to reproduce themselves sufficiently. These cells actually matured too early instead of continuing to replicate as they should have. Consequently, in adulthood, there were not enough mature cells, leaving many axons without insulation.

The researchers study zebrafish because they are excellent models of the vertebrate nervous system. Their embryos are transparent and mature outside the body, making them useful for observing developmental processes. Gpr56 belongs to a large class of cell receptors that are common targets for many commercially available drugs, making the protein attractive for further research. The investigators pointed out its possible relevance in treating diseases associated with a lack of myelin, with a particular interest in multiple sclerosis (lat. Sclerosis multiplex).

There are areas where the central nervous system has lost its myelin. At least part of the problem is that the precursor myelin-producing cells are recruited to that area, but they fail to become adult cells capable of producing nerve cell insulation. Now, the team has evidence that Gpr56 modulates the switch from precursor to the adult cell. In theory, if the precursor cells can be pushed to mature into adulthood, they may become capable of producing myelin. Possible future work includes using the zebrafish model system as a drug-screening tool to search for small molecules that may flip that switch.