The study, published in the Dec. 12, 2003, issue of the journal Science, solves a long-standing scientific mystery. It may also help restore function to people with paralyzing spinal cord injuries.
"This is the first guidance mechanism that regulates growth of nerve cells up and down the spinal cord," said Yimin Zou, Ph.D., assistant professor of neurobiology, pharmacology and physiology at the University of Chicago.
"This is exciting to scientists because these neurons are the primary model system we use to understand assembly of the nervous system," he said. "It's exciting to clinicians because it could help regenerate damaged axons in the central nervous system."
The study focused on commissural neurons, which are found in the spinal cord. These neurons receive sensory signals such as pain, heat or cold from the primary neurons that reach from the hands or feet, for example, to the spinal cord. The commissural neurons relay those signals up the spinal cord to the nerve cells that process the information in the brain.
In a meticulous series of experiments with rats, Zou and colleagues show that a gradient of chemoattractant(s) along the spinal cord, probably formed by one or multiple Wnt proteins, lures growing commissural neurons toward the brain.
The Wnt family of proteins carry signals from cell to cell, regulating the interactions between cells during many development processes. Wnt proteins bind to receptors of the "Frizzled" family on the cell surface.
In the Science paper, Zou and colleague show that the Wnt gradient is detected by a receptor known as Frizzled3, found at the tips of these growing neurons. Commissural axons in Frizzled3-deficient mice (generously provided by Jeremy Nathans of
Contact: John Easton
University of Chicago Medical Center