Scientists Discover The Molecular Switch For Nerve Cells' Insulating Jelly Rolls

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

Using a sophisticated system for growing nerve cells inlaboratory dishes, the team identified a gene called neuregulin as themyelin signal. This signal directs Schwann cells, the nervous system'scellular architects, to build elaborate sheaths of myelin around theaxons of nerve cells. Axons are the long cable-like arms of nerve cellsthat send messages to other cells. The construction of myelin sheathhas been called one of the most beautiful examples of cellspecialization in nature.

Myelin forms the so-called white matter in the nervous systemand constitutes 50 percent of the weight of the brain. It is also animportant component of the spinal cord, and of nerves in other parts ofthe body. It has been known for almost 170 years that there are twokinds of axons --one is wrapped in myelin and appears white and theother is not and appears gray. Myelinated axons transmit messages inthe nervous system up to 100 times faster than their unmyelinatedcousins and are critical for proper neurological function. However, itwasn'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 wasimplicated in determining the thickness of the myelin sheath aroundaxons; however, until now it wasn't clear whether the gene alsoswitched on production of the sheath.

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

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

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

Dr. Salzer's study was supported by grants from the NationalInstitutes of Health and the National Multiple Sclerosis Society, amongother groups.