What regulates the winding of the myelin sheath

Regulator of myelin production discovered in the nervous system

Scientists at the Max Planck Institute for Experimental Medicine have discovered a molecular growth factor that controls the extent of myelin formation in nerve cells

In the nervous system of vertebrates, the covering of the nerve fibers by so-called "myelin sheaths" is essential for the rapid and accurate transmission of nerve impulses. In a healthy organism, the thickness of these myelin layers is always proportional to the strength of the nerve fibers. A team of scientists at the Max Planck Institute for Experimental Medicine led by Prof. Klaus Armin Nave has now discovered in mice that this proportionality is regulated by the so-called axonal neuregulin-1 factor (Nrg1). Depending on how much of this signal is expressed on the surface of nerve cells, the stronger or weaker the Schwann cells, which form the myelin protective layer around the nerve fibers, grow (Science, March 26, 2004). The discovery of this growth factor is of fundamental importance for a better understanding of the body's own repair processes and in particular for therapies for demyelinating diseases in humans, such as multiple sclerosis.

Myelin works in our nervous system as an electrical insulator for the ion currents in the nerve cell process (axon). It is therefore directly responsible for the high speed of the transmission of stimuli. Myelin sheaths arise through a growth process of highly specialized glial cells along both thin and thick axons. In the peripheral nervous system, it is Schwann cells that spiral around the axon. The thickness of the resulting myelin sheath is surprisingly always proportional to the thickness of the wrapped axon itself. For almost a hundred years, the question has therefore been how the Schwann cells can "know" whether they are currently wrapping a thick or a thin axon. to then grow accordingly differently.

Scientists at the Max Planck Institute for Experimental Medicine have now succeeded in uncovering an important mechanism of this axon-glia communication with the help of transgenic mice and mouse mutants. Afterwards, nerve cells (neurons) express a growth factor, neuregulin-1, and present it to the myelin-forming Schwann cells on the surface of their nerve endings (axons), which they then recognize through receptor proteins. The researchers found that it is the amount of neuregulin-1 factor that biochemically tells Schwann cells what diameter the axon to be wrapped is about. Because thick axons have a larger surface with more neuregulin-1 than thinner nerve endings.

If the axonal neuregulin-1 signal in a mouse mutant is experimentally reduced by half, the myelin-forming tail cells receive incorrect information about the diameter of the axon. In fact, they then form less myelin in the experiments, just for a smaller-caliber axon. As a result, however, the thick axon is less insulated and the nerve conduction velocity in this mouse mutant is reduced.

Conversely, the Max Planck scientists observed exactly the opposite in transgenic mice, which they had induced by overexpression of this gene to produce an excessive amount of the axonal neuregulin-1 signal in their neurons. This misinformation led to an excessive growth of the Schwann cells and a pathologically excessive myelin formation (see Fig. 1), which cannot normally be observed in mice.

The researchers suspect that a similar signal system has developed between axons and glial cells in the central nervous system and controls myelin formation. Investigating this is the subject of their next projects.

Michael Sereda, neurologist at the University of Göttingen and one of the authors of the study, says: "The discovery of this growth factor, which controls the amount of myelin formation in the nervous system, is of fundamental importance and also raises new hopes. Further experiments should show whether you can with Neuregulin, we can specifically support repair processes in the diseased nervous system and use them for therapies, for example for multiple sclerosis. But there is still a long way to go. "