Complex wiring of the nervous system may rely on a just a handful of genes and proteins

Discovery provides clues to development of neurological diseases and cancer

Samuel Pfaff.

Researchers at the Salk Institute have discovered a startling feature of early brain development that helps to explain how complex neuron wiring patterns are programmed using just a handful of critical genes. The findings, published February 3 in Cell, may help scientists develop new therapies for neurological disorders, such as amyotrophic lateral sclerosis (ALS), and provide insight into certain cancers.

The Salk researchers discovered that only a few proteins on the leading edge of a motor neuron's axon - its outgoing electrical "wire" - and within the extracellular soup it travels through guide the nerve as it emerges from the spinal cord. These molecules can attract or repel the axon, depending on the long and winding path it must take to finally connect with its target muscle.

"The budding neuron has to detect the local environment it is growing through and decide where it is, and whether to grow straight, move to the left or right, or stop," says the study's senior investigator, Sam Pfaff, a professor in Salk's Gene Expression Laboratory and a Howard Hughes Medical Institute investigator.

"It does this by mixing and matching just a handful of protein products to create complexes that tell a growing neuron which way to go, in the same way that a car uses the GPS signals it receives to guide it through an unfamiliar city," he says.

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