Gradient guides nerve growth down spinal cord

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Gradient guides nerve growth down spinal cord

15 Aug 2005

http://www.medicalnewstoday.com/medicalnews.php?newsid=29132

The same family of chemical signals that attracts developing sensory

nerves up the spinal cord toward the brain serves to repel motor

nerves, sending them in the opposite direction, down the cord and

away from the brain, report researchers at the University of Chicago

in the September 2005 issue of Nature Neuroscience (available online

August 14). The finding may help physicians restore function to

people with paralyzing spinal cord injuries.

Growing nerve cells send out axons, long narrow processes that search

out and connect with other nerve cells. Axons are tipped with growth

cones, bearing specific receptors, which detect chemical signals and

then grow toward or away from the source.

In 2003, University of Chicago researchers reported that a gradient

of biochemical signals known as the Wnt proteins acted as a guide for

sensory nerves. These nerves have a receptor on the tips of their

growth cones, known as Frizzled3, which responds to Wnts.

In this paper, the researchers show that the nerves growing in the

opposite direction are driven down the cord, away from the brain,

under the guidance of a receptor, known as Ryk, with very different

tastes. Ryk sees Wnts as repulsive signals.

" This is remarkable example of the efficiency of nature, " said Yimin

Zou, Ph.D., assistant professor of neurobiology, pharmacology and

physiology at the University of Chicago. " The nervous system is using

a similar set of chemical signals to regulate axon traffic in both

directions along the length of the spinal cord. "

It may also prove a boon to clinicians, offering clues about how to

grow new connections among neurons to repair or replace damaged

nerves. Unlike many other body components, damaged axons in the adult

spinal cord cannot adequately repair themselves. An estimated 250,000

people in the United States suffer from permanent spinal cord

injuries, with about 11,000 new cases each year.

This study focused on corticospinal neurons, which control voluntary

movements and fine-motor skills. These are some of the longest cells

in the body. The corticospinal neurons connect to groups of neurons

along the length of spinal cord, some of which reach out of the

spinal cord. They pass out of the cord between each pair of vertebrae

and extend to different parts of the body, for example the hand or

foot.

Zou and colleagues studied the guidance system used to assemble this

complex network in newborn mice, where corticospinal axon growth is

still underway. Before birth, axons grow out from the cell body of a

nerve cell in the motor cortex. The axons follow a path back through

the brain to the spinal cord.

By the time of birth, the axons are just growing into the cord.

During the first week after birth they grow down the cervical and

thoracic spinal cord until they reach their proper position, usually

after seven to ten days.

From previous studies, Zou and colleagues knew that a gradient of

various Wnt proteins, including Wnt4, formed along the spinal cord

around the time of birth. Here they show that two other proteins,

Wnt1 and Wnt5a are produced at high concentrations at the top of the

cord and at consecutively lower levels farther down.

They also found that motor nerves are guided by Wnts through a

different receptor, called Ryk, that mediates repulsion by Wnts.

Antibodies that blocked the Wnt-Ryk interaction blocked the downward

growth of corticospinal axons when injected into the space between

the dura and spinal cord in newborn mice.

This knowledge, coupled with emerging stem cell technologies, may

provide the most promising current approach to nervous system

regeneration. If Wnt proteins could be used to guide transplanted

nerve cells -- or someday, embryonic stem cells -- to restore the

connections between the body and the brain, " it could revolutionize

treatment of patients with paralyzing injuries to these nerves, " Zou

suggests.

" Although half the battle is acquiring the right cells to repair the

nervous system, " he said, " the other half is guiding them to their

targets where they can make the right connections. "

" Understanding how the brain and the spinal cord are connected during

embryonic development could give us clues about how to repair damaged

connections in adults with traumatic injury or degenerative

disorders, " Zou added.

The National Institute of Neurological Disorders and Stroke, the

Schweppe Foundation, the Packard ALS Center at s Hopkins,

the University of Chicago Brain Research Foundation and the Jack

Peripheral Neuropathy Center supported this study.

Additional authors include Yaobu Liu, Jun Shi. Chin-Chun Lu, and

Lyuksyutova of the University of Chicago, and Zheng-Bei Wang and

Xuejun Song of the College Research Institute in Dallas Texas.

Easton

University of Chicago Medical Center

uchospitals.edu