New Brakes for Nerve Growth

Scientists have found that proteins that stimulate the growth and survival of nerve cells as they build the brain do more than just that. A report, published tomorrow in the journal Neuron, suggests that the proteins, which are called neurotrophins, can also inhibit growth, providing the controls necessary to sculpt the brain.

To figure out how the neurotrophins might shape the brain, Kimberly McAllister, Lawrence Katz, and Donald Lo, all at Duke University, examined the effects of two of them, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), on slices of the cerebral cortex from the developing brains of young ferrets. In their earlier work, they had added extra BDNF to a particular part of the developing cortex known as layer 4 and found that it caused a growth spurt of the dendrites, the treelike structures on neurons that receive the signals from other neurons. The size and shape of the so-called dendritic tree is crucial to the function of a neuron: It controls the amount of input from other neurons that a neuron can receive.

The team decided to verify that finding by treating tissue slices from developing ferret brains with a chemical that blocks BDNF's activity. As expected, when they did this, the dendrites in cortical layer 4 didn't grow. The surprise came when they added molecules to block NT-3, simply as a control. Because adding NT-3 doesn't boost dendrite growth, they didn't expect much to happen. Instead, the dendrites "went wild," says Katz, and proliferated just as if they had received a shot of BDNF. Further experiments showed that BDNF spurs the growth, and NT-3 keeps it in check--a previously unknown role for a neurotrophin. The researchers got an even bigger surprise, though, when they looked at what happens in another cortical layer, layer 6. "It worked out to be the exact same story, but with opposite polarities," says Katz. In layer 6, NT-3 promotes dendrite growth and BDNF opposes that effect.

This finding suggests that neurotrophic factors "may be in a large part what is responsible" for the sculpting of dendrites, says developmental neurobiologist William Snider, of Washington University in St. Louis. "It is hard to drive a car with just an accelerator, and it is hard to make a dendritic tree with just growth promotion," says Katz. "You need to have something to prevent runaway growth." Now it seems that neurotrophins in some cases act as both the accelerator and the brakes.