Genes Keep Neurons' House in Order

Out of line.Axons in Caenorhabditis elegans stray from their proper places (arrow) when ZIG proteins are removed.

Scientists have spent decades teasing apart the complex signals that guide axons--the long extensions that allow neurons to communicate with distant cells--to their correct destinations and help them make the right connections. But most developmental biologists assumed that the signaling was complete once the worm reached the larval stage.

Neuroscientists Oliver Hobert and Oscar Aurelio of Columbia University and David Hall of the Albert Einstein College of Medicine, both in New York City, were examining expression patterns of unknown genes in a family known for its role in neural development. To their surprise, they noticed that six genes kicked into action late in the game--in the larvae and the adult, after embryonic development was complete. The genes, dubbed the zig genes, are expressed in a neuron called PVT in the larval worm's ventral nerve cord. PVT's axon extends the length of the worm's body and secretes proteins that guide other axons to the correct place in the growing nervous system.

To test the genes' function, Aurelio used a laser to kill PVT neurons in early-larval-stage worms. Two days after surgery, he found that in nearly a third of the treated worms, axons had wandered across the worm's midline to the wrong side of the nerve cord. Then Aurelio and his colleagues examined a strain of worms lacking zig-4. After these worms developed into larvae, a subset of axons wandered across the midline. Hobert isn't sure what zig genes do in adults, but suspects that they keep axons in place elsewhere in the body.

Similar maintenance molecules will turn up in other animals--perhaps even in humans, predicts developmental neuroscientists Barry Dickson of the Institute of Molecular Pathology in Vienna, Austria. "If keeping the wires neat and tidy matters for a worm, it's going to matter for higher animals, too."

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