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Growing neurons use silencing mechanism to avoid disastrous tug-of-war

March 9, 2001—Just as traffic signals switch off the red light when the green light comes on, the tips of growing nerve cells protect themselves from being led astray by switching off their sensitivity to an attractant protein when activating sensitivity to a repellent protein. This interlocking fail-safe mechanism might be a basic strategy used throughout the central nervous system to avoid the disastrous consequences of a tug-of-war between signals that attract and repel neurons. The discovery might also help explain why spinal cord neurons cannot be easily induced to regenerate after injury, said the researchers.

The discovery was reported by Howard Hughes Medical Institute investigator Marc Tessier-Lavigne and lead author Elke Stein in the March 9, 2001, issue of the journal Science.

Neurons wire themselves into networks by extending cable-like axons that grow toward specific targets in the nervous system. An axon’s path towards a target neuron is steered by growth cones in the tip of the axon that receive cues about the best path to follow from chemical attractants and repellents secreted by cells in the nervous system.

Tessier-Lavigne and his colleagues at the University of California, San Francisco, had previously identified a key attractant protein called netrin-1. Netrin-1 exerts its influence on growth cones by plugging into a receptor called DCC that nestles in the cell membrane. Conversely, a repellent protein called Slit triggers axons to grow away from a site by plugging into a receptor called Robo. Thus, a growing axon is attracted by netrin to a target way station in the spinal cord and then repelled from it toward the next way station by Sli
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
8-Mar-2001


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