New technology shows axons are extremely sensitive to directional cues

Researchers at Georgetown University have developed a novel technology to precisely measure the sensitivity of nerve fibers that wire up the brain during development. Through use of this technology, they discovered that these fibers, or axons, possess an incredible sensitivity to molecular guidance cues that direct the axon’s route to its desired destination in the brain. Their findings are described in the June issue of Nature Neuroscience.

Similar to connecting your PC, monitor, mouse and printer correctly to make all computer parts work, the developing brain needs a series of critical wiring connections to be made for it to function properly. But, unlike computers that come with a user and troubleshooting manual, nerve fibers called axons must follow molecular cues to find the right targets.

Much work has been done to understand what molecules are involved in this process, called axonal guidance. However, no technology until now allowed researchers to create a controllable, stable gradient with which one could measure the sensitivity of axons to gradients, and how that sensitivity can impact and guide the development of connections in the brain.

“I was curious about the physics of this wiring up process, which led our lab in a different direction than others who study axonal guidance,” said Geoff Goodhill, PhD associate professor of neuroscience at Georgetown University Medical Center. “Once we had created a stable environment and could control molecular gradients, we were amazed to discover just how sensitive axons are to tiny changes in the concentration of molecular cues. We’ve found that a difference in concentration of a single molecule across the tip of an axon can measurably impact the direction in which the axons grow.”

Goodhill notes this physics-based approach to understanding gradients affect axons may eventually assist researchers who study how the nervous system regenerates after injury. “Clearly, the more we understand about what guides connectivity normally, the greater chance there is of figuring out how connections can be regrown after they’ve been lost.”

The technology may also have applications outside the realm of neuroscience. “In cancer, and other biological fields where cell migration in important, we think our new technology may be useful for studying movement in response to gradients,” said Goodhill.

The team has plans to conduct further research on molecular gradients and axonal guidance by using time lapse imaging, and studying if axons are as sensitive to repulsive molecular cues that push axons away from particular regions.

Goodhill conducted this research with Georgetown collaborators Will Rosoff, PhD in Neuroscience, Jeffery Urbach, PhD, Mark Esrick, PhD and Ryan McAllister, PhD in Physics, and Linda J. Richards, PhD, of the University of Maryland. Their research was supported by the National Institutes of Health, National Science Foundation, and Whitaker Foundation.

Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through our partnership with MedStar Health). Our mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis–or “care of the whole person.” The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, and the world renowned Lombardi Comprehensive Cancer Center.