Simple Chemical Switch Steers Migrating Neurons

September 9,1998—In an embryo's developing brain and spinal cord, the growing ends of nerve cells, called axons, travel great distances to make precise connections with other neurons. Without such accurate connectivity, the nervous system would never wire properly.

An axon's path towards a target neuron is steered by growth cones that are located in the tip of the axon. These growth cones receive cues about the best path to follow from chemical attractants and repellents secreted by cells in the central nervous system.

Until recently, scientists assumed that type of neuron and the unique chemical receptors found on its surface determined whether a neuron is attracted to or repelled by a given guidance chemical. Now, HHMI investigator Marc Tessier-Lavigne at the University of California, San Francisco, working with Mu-ming Poo and colleagues at the University of California, San Diego (UCSD), has found that a single chemical cue can either attract or repel, depending on the growth cone's internal status. This research is reported in the September 4, 1998, issue of the journal Science.

This work, says Tessier-Lavigne, may hold promise for regenerating nerves damaged by spinal cord injury. It also provides potentially important clues for understanding disorders of neuronal migration, which may be responsible for childhood epilepsy, forms of mental retardation, and possibly dyslexia and schizophrenia.

The researchers found that two key signaling chemicals, cyclic AMP and cyclic GMP, located in the growth cone, act as switches. In general, increasing levels of these cyclic nucleotides promotes attraction, while lowering levels favors repulsion. Thus, both attraction and repulsion share a common chemical switch.

In studying spinal cord neurons cultured from frog embryos, the investigators found evidence of two steering-related circuits within the growth cones, one responding to cyclic AMP, the other to cyc

Contact: Jim Keeley
Howard Hughes Medical Institute

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