Molecular switch that turns on the production of myelin

Scientists at New York University School of Medicine report in a new study that they have identified the molecular switch that turns on the production of myelin, the fatty insulation around nerve cells that ensures swift and efficient communication in the nervous system.

The study, published in the September 1, 2005, issue of the journal Neuron, may provide a new avenue for treating nervous system diseases such as multiple sclerosis, which are associated with damage to myelin.

A team led by James L. Salzer, M.D., Ph.D., Professor of Cell Biology and Neurology at NYU School of Medicine, identified the long-sought factor that determines whether or not nerve cells will be wrapped in thick layers of myelin, producing the biological equivalent of a jelly roll.

Using a sophisticated system for growing nerve cells in laboratory dishes, the team identified a gene called neuregulin as the myelin signal. This signal directs Schwann cells, the nervous system's cellular architects, to build elaborate sheaths of myelin around the axons of nerve cells. Axons are the long cable-like arms of nerve cells that send messages to other cells. The construction of myelin sheath has been called one of the most beautiful examples of cell specialization in nature.

Myelin forms the so-called white matter in the nervous system and constitutes 50 percent of the weight of the brain. It is also an important component of the spinal cord, and of nerves in other parts of the body. It has been known for almost 170 years that there are two kinds of axons --one is wrapped in myelin and appears white and the other is not and appears gray. Myelinated axons transmit messages in the nervous system up to 100 times faster than their unmyelinated cousins and are critical for proper neurological function. However, it wasn't known what actually initiated myelin production.

The neuregulin gene encodes a growth protein made by neurons. Last year a group of German scientists discovered that it was implicated in determining the thickness of the myelin sheath around axons; however, until now it wasn't clear whether the gene also switched on production of the sheath.

In a series of experiments, Dr. Carla Taveggia, the first author of the study and an NYU research scientist, together with collaborators at NYU, Columbia University College of Physicians and Surgeons, and other institutions, showed that unmyelinated neurons do not possess an active neuregulin gene and that myelinated neurons do. In the first set of experiments, they transplanted unmyelinated axons from the peripheral nervous system (outside of the brain and spinal cord) of embryonic mice into laboratory dishes. They then added Schwann cells to the dishes. They observed that the Schwann cells sat on the axons and did not produce any myelin.

In the next set of experiments, they inserted the neuregulin gene into the unmyelinated axons. Instead of just sitting on the axons, the Schwann cells now produced thick myelin sheaths around them. So it appears that the gene instructs the Schwann cells to build the myelin wrap.

Dr. Salzer's group is investigating whether neuregulin has the same effect on myelination in the central nervous system--the brain and spinal cord. If so, it may one day be possible to enhance or fix damaged spinal cords and brain tracts that have lost their myelin due to injury or disease by transplanting into, or turning on, a functioning neuregulin gene in nerve cells. "Is it possible that this same switch can reprogram a nerve cell that has lost myelin due to injury or disease to repair itself? That is a key question that our laboratory and others are now actively trying to answer," he says.