NEW YORK (Feb. 19, 2008) -- A longstanding puzzle in neurodevelopment may have yielded up a key secret.
A team led by scientists at Weill Cornell Medical College says they have determined how events at the very tips of the developing neuron's long, skinny axon affect gene transcription back in the cell's distant nucleus.
The study also revealed the first-ever evidence of a transcription factor -- proteins that influence gene activity -- working outside the cell's nucleus.
The findings, published in the Feb. 1 issue of Nature Cell Biology, could bring neuroscientists a much better understanding of how nerve cells grow and connect during healthy development, and how these processes might go astray in neurological disease.
"We have found a process whereby the growth cone at the developing axon's tip sends key signals back to the cell nucleus to ensure the neuron's survival," explains senior study author Dr. Samie R. Jaffrey, associate professor of pharmacology at Weill Cornell Medical College. "In this way, the human nervous system develops over time, choosing viable neural pathways over neurological 'dead ends.' This process hinges on the type of communication between the growth cone and the nucleus that we now describe."
As Dr. Jaffrey explains, the developing fetus carries many times more neurons than it will retain after birth. These newly formed neurons send out long branches called axons that seek specific targets -- a toe, for example, or a kidney or an eye. In recent years, scientists discovered that as the axon reaches its target -- which may be many centimeters away from the nucleus -- it senses a signal called nerve growth factor (NGF), which is made by target tissues.
"Most axons never make it to their proper destination and the neurons die off in a preprogrammed way," Dr Jaffrey says. "But the axons that correctly navigate to their destinations detect NGF which 'says' to the neuron 'No, you've mad
|Contact: Andrew Klein|
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College