Scientists Crack Motor Neuron Code
Columbia neuroscientists have deciphered a motor neuron code that one day may help in attempts to restore movement in people with diseases like ALS (Lou Gehrig's disease) and Spinal Muscular Atrophy (SMA) or spinal cord injuries.
Motor neurons within the spinal cord connect to the body's muscles and are responsible for all of our movements, from running a marathon to raising an eyebrow. In patients with ALS and SMA motor neurons die over time and eventually cause paralysis and death.
"If cell replacement therapies are to work in the future it may not be enough to make new motor neurons," says Thomas Jessell, Ph.D., professor of biochemistry and molecular biophysics and member of the Center for Neurobiology and Behavior. "We will have to understand how to connect the neurons to the right muscles in order to restore movement."
The connections motor neurons make are established during development, when newly generated motor neurons in the spinal cord send axons out to "wire" the animal's muscles. This wiring process is not random each motor neuron has already formed an allegiance to a particular muscle before the axons start growing.
In a study published in the Nov. 4 issue of Cell, Dr. Jessell and postdoctoral researcher Jeremy Dasen, Ph.D., describe just how these allegiances are formed with a code based on 21 different Hox genes, which encode proteins that regulate gene expression.
They discovered that different combinations of the Hox genes assign muscle targets to all the different motor neurons in the spinal cord. The code first constricts certain neurons to limb muscles, then assigns groups of motor neurons to connect with individual muscles within a limb.
Though the code generates 100 different types of motor neurons, there is still space in the code to produce even more. "This is still conjecture, but the sheer number of Hox genes suggests that they may also impart identity to interneurons and sensory neurons," Dr. Jessell says. "The more we understand the basic workings of the entire locomotor circuit, the better chance there is of developing regenerative strategies to restore movement." The research was supported by the NINDS and Project ALS.