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Receptor Helps Neurons Grow in Right Direction

Science Update

Understanding the anatomy of communication in the developing nervous system can help scientists find out where it goes awry.

Researchers have discovered a receptor for a key protein that helps guide certain nerve cells into the correct position as the nervous system develops — a vital part of a process that enables the brain to receive sensory input from the environment and to send messages to the rest of the body via the spinal cord.

The receptor, Boc, helps guide segments of nerve cells called commissural axons — projections extending from the cells — into place as the axons grow long enough to reach from the bottom of the spinal cord to the brain. Ultimately, the axons serve as highways that carry electrical impulses in the nervous system, the biological messages crucial to brain function. If these axon highways are "built" in the wrong directions, electrical impulses might reach the wrong destinations, with potentially profound implications for nervous-system function.

Lead researcher Susan K. McConnell, Ph.D. (Stanford University), and colleagues found that when the growing tips of the axons bring the Boc receptor close to a protein called Sonic Hedgehog (Shh) found in areas around nerve cells, Boc and Shh bind together. This vital interplay causes the axons to turn toward the correct positions in their long journeys toward the brain.

The scientists who made this discovery, using the developing rodent brain as a model, previously had shown that Shh plays an essential role in guiding commissural axons into place. Until now, it wasn't known which receptor enabled Shh to exert its effects. McConnell and colleagues from Stanford University, the Institute de Rechereches Cliniques de Montreal, University of Montreal, and Genentech, published their results in the November 16 issue of Nature.

The researchers also found that a related protein, Cdon, is another receptor for Shh, but doesn't appear to play a part in directing the axons. It may play another important, but as yet undiscovered, role in development.

Understanding how the nervous system develops can help scientists understand where and how to intervene when defects occur in the brain's wiring.

Okada A, Charron F, Morin S, Shin DS, Wong K, Fabre PJ, Tessier-Lavigne M, McConnell SK. Boc is a receptor for sonic hedgehog in the guidance of commissural axons . Nature 444, 369-373 (16 November 2006).