These extreme rates of growth are not consistent with the current understanding of the limitations of axon growth. "Proteins necessary to sustain this growth are somehow correctly brought to sites along the axon faster than conceivable rates of transport," notes Smith. The team suggests two possible mechanisms to explain this: increasing transport to a very fast rate or making the necessary proteins at the site, proximal to the growing axons. Smith believes that this form of growth commonly occurs in nature. "For example, it can be inferred that axons in a blue whale's spine grow more than three centimeters a day and in a giraffe's neck at two centimeters a day at peak growth."

The team also found that they had to condition the axons to grow in an extreme way. "Although they can handle enormous growth, you can't just spring it on them," explains Bryan Pfister, PhD a post-doctoral fellow in Smith's lab and coauthor of the study. "If we ramp up the stretch rate too fast, the axons will snap." From this the team surmises that in nature animals must grow at a metered pace, which allows for constant feedback and conditioning.

It has been well established that axons initially grow out from neurons and follow a chemical stimulus to connect with another neuron. However, once the axon has reached its target a relatively unknown form of stretch-growth must ensue as the animal grows. Mechanical changes in the growing brain, spine, and other bones are the starting point for natural stretch-growth in axons. "We know that it's not tension on the neuron itself, but tension on the axon," says Smith. "It's deformation, a pulling on the axon." At this point, it is unclear what receptors and cell signaling pathways are involved to get the process started, but from this and previous studies the investigators do report that the signal is from a mechanical stimulus along the length of the axon as opposed to a chemical stimulus. "The stretch is coming from
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
7-Sep-2004