But how does this critical information get passed from the growth cone at the tip of the axon back to the cell's "command center," the nucleus?
"That was the central mystery we sought to clear up in this work," Dr. Jaffrey says.
To do so, his team examined axonal growth cones for messenger RNA (mRNA) -- bits of genetic material that help produce specific proteins. The team used an innovative new technique developed by study lead author Dr. Llewellyn J. Cox, a postdoctoral researcher in Dr. Jaffrey's lab. He coaxed axons to grow in such a way that the scientists were able to sample mRNA in the growth cones alone.
"By doing so, we were able to build a library of mRNA found in those growth cones," Dr. Cox said.
The experiment yielded one big surprise: a type of mRNA that produces a transcription factor called CREB.
"Prior research elsewhere has shown that CREB is essential to neuronal survival," Dr. Jaffrey says. "But no one had ever thought it might be active in the axon."
The team next used cutting-edge fluorescent technology to track CREB's activity in the presence of the "survival signal," NGF.
"We watched CREB being produced in the growth cone and then saw it travel back to the nucleus," Dr. Jaffrey says. "This was astounding -- it suggested that the axonally-synthesized protein could have a role in the nucleus, a very long distance away."
It is this axonally produced CREB that appears to be key to switching off the neuron's self-destruct mechanism, he says. "The axonal CREB enters the nucleus, where it induces gene expression that ensures that the developing neuron will survive," Dr. Jaffrey says.
This was confirmed in a later experiment where the team selectively abolished CREB mRNA from the axons but not the rest of the neuron. "When that happened, the neurons died,
|Contact: Andrew Klein|
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College