Biologists Discover Genes That
Repair Nerves After Injury

Science News
Blog     Cite
Save   Email   Print   Share
Biologists Discover Genes That Repair Nerves After Injury
ScienceDaily (Sep. 21, 2011) — Biologists at the University of California, San Diego have
identified more than 70 genes that play a role in regenerating nerves after injury, providing
biomedical researchers with a valuable set of genetic leads for use in developing
therapies to repair spinal cord injuries and other common kinds of nerve damage such as
stroke.
________________________________________
See Also:
Health & Medicine
•        Genes
•        Nervous System
•        Disability
Mind & Brain
•        Brain Injury
•        Neuroscience
•        Parkinson's
Reference
•        Sensory neuron
•        Pupillary reflex
•        Axon
•        Healing
In the September 22 issue of the journal Neuron, the scientists detail their discoveries
after an exhaustive two-year investigation of 654 genes suspected to be involved in
regulating the growth of axons -- the thread-like extensions of nerve cells that transmit
electrical impulses to other nerve cells. From their large-scale genetic screen, the
researchers identified 70 genes that promote axon growth after injury and six more genes
that repress the re-growth of axons.
"We don't know much about how axons re-grow after they're damaged," said Andrew
Chisholm, a professor of biology at UC San Diego. "When you have an injury to your
spinal cord or you have a stroke you cause a lot of damage to your axons. And in your
brain or spinal cord, regeneration is very inefficient. That's why spinal cord injuries are
basically untreatable."
Chisholm and UC San Diego biology professor and HHMI Investigator Yishi Jin headed
the collaborative research team, which also included researchers from the University of
Oregon.
While scientists in recent decades have gained a good understanding of how nerve cells,
or neurons, develop their connections in the developing embryo, much less is known
about how adult animals and humans repair -- or fail to repair -- those connections when
axons are damaged.
"There are many processes not involved in early development that are involved in
switching the neurons to this re-growth mode," said Chisholm. "In essence what we
found are genes that people had not suspected previously to be part of this process."
Of particular interest to the UC San Diego biologists are the six genes that appear to
repress the growth of axons.
"The discovery of these inhibitors is probably the most exciting finding," said Chisholm,
because identifying and eliminating the inhibiting factors to the re-growth of axons could
be just as essential as the biochemical pathways that promote axon re-growth in
repairing spinal cord injuries and other kinds of nerve damage.
The scientists were also surprised to learn that some of the genes they found to be
involved in the re-growth of axons were known to have other functions, such as regulating
the release of neurotransmitters.
"This was in large part unexpected," said Chisholm. "These genes had not been
implicated in the re-growth of axons before."
To find the 76 genes, the researchers conducted painstaking experiments on more than
10,000 tiny laboratory roundworms known as C. elegans. The first step involved
developing genetic mutants of these transparent roundworms for each one of 654 genes
that were suspected to play a role in the regulation of axon regrowth in worms, fruit flies
and mice. They then labeled the roundworm neurons with green fluorescent protein and,
with a precise surgical laser, damaged a specific axon.
"The goal was to study this process in its simplest form," said Chisholm. "Because the
animals are essentially transparent, we can see the axons expressing this green
fluorescent protein."
By examining the re-growth, or lack of growth, of the damaged axon 24 hours later, the
scientists were then able to determine which of these 654 genes were actually important
to axon re-growth.
Chisholm said that while the 76 genes identified are believed to have similar roles in
mammals as well as roundworms, because their functions were "conserved" by the
organisms through evolution, he and his research team are now collaborating with other
investigators to conduct experiments on mice to verify this connection and determine
which of these genes are the most critically important.
"Worms are clearly different from mammals," he added. "But there will be a core of
conserved molecules doing the same job."
In addition to Chisholm and Jin, the UC San Diego biologists involved in the study were
Lizhen Chen, Zhiping Wang, Anindya Ghosh-Roy, Thomas Hubert, Dong Yan, and Zilu
Wu. Sean O'Rourke and Bruce Bowerman from the University of Oregon were also part of
the team.
The research project was supported by grants from the National Institutes of Health and
the Howard Hughes Medical Institute.