Lipid Signaling Modifies Axon Connections

Posted by Sam Maddox in Research News on August 31, 2015 # Research

A research paper came out a few days ago about how spinal cord axons, what many of us think of as nerve fibers, are guided to make connections exactly where they are supposed to.

That issue – connecting – is a primary concern in development, as the system is formed with elegance and precision, and again after spinal cord injury, where it doesn’t happen quite so efficiently. Now comes a group from Japan that has found a clue that might help scientists understand axon positioning, and maybe, lead them to develop new therapies.

Proteins are essential, of course, for signaling various biological activities. A group at the RIKEN Brain Science Institute in Japan reports that in addition to proteins, lipids are also necessary for guiding axons.

Published in Science, the paper is titled, “Glycerophospholipid regulation of modality-specific sensory axon guidance in the spinal cord.” The study shows how a phospholipid released by glial cells — cells in the nervous system that support neurons -- controls the positioning of sensory neurons within the spinal cord.

From a very nicely rendered Riken press release:

Axons -- the long extensions of neurons -- are the roads that allow neural information to travel from place to place, and their pathways are typically specific for each of our senses, eventually reaching different places in our brains and spinal cords. During development, the growth of axons is guided by a patterned distribution of molecules that either attract or repel them, forcing them to go in the proper direction.

"While many proteins are known to direct axon growth and network formation," says Senior Team Leader Hiroyuki Kamiguchi, "We discovered that glial cells have the ability to release membrane structural lipids in specific patterns that can then control axon migration and neuron organization. In this case, we found that a lipid called LysoPtdGlc has a major role in separating axons of pain- and position-sensing neurons from each other."

Here’s how they explain this. Sensory information going to the brain from our skin and muscles has to pass through the spinal cord. Axons carrying sensory detail enter the spinal cord together, but soon separate. “Those responsible for feelings of pain -- nociception -- travel along the side of the spinal cord, while those that let us know where our muscles are -- proprioception -- travel in a neighboring region closer to the midline,” said Kamiguchi.

So apparently, when axons of pain-sensing neurons run into LysoPtdGlc, they are repulsed away from the midline area, forced to travel in the more lateral region of the spinal cord.

They tested this repulsion idea by blocking access to the lipid with an antibody; that prevented pain-sensing neurons from being repelled. They then injected the antibody into the spinal cord of chick embryos. Again, the axons of pain-sensing neurons were no longer repelled. They migrated into the region on the spinal cord reserved for position-sensitive neurons.

Kamiguchi and his group discovered a protein receptor that responded well to LysoPtdGlc, and confirmed that this protein is also expressed in the spinal cord. One might speculate that knowing how to manipulate the lipid-related signals could drive axons toward optimal targets. In the case of connections related to pain, such targeting would have clear advantages.

"With these findings" says Kamiguchi, "we can begin to investigate whether this lipid-based signaling system can be a therapeutic target for spinal cord injury. I hope that our success here can facilitate interdisciplinary collaboration aimed at tackling other problems in biomedical research."

The National Paralysis Resource Center website is supported by the Administration for Community Living (ACL), U.S. Department of Health and Human Services (HHS) as part of a financial assistance award totaling $8,700,000 with 100 percent funding by ACL/HHS. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by ACL/HHS, or the U.S. Government.