or how effective NGF can be to simulate a cell’s drive to survive. When they plugged in the model, it showed that over time-about 100 days or so-about half of the cells manage to survive, while the other half die.
But, in the developing mouse embryo, nerve cells that die do so over the course of two to three days just before birth. “So then we considered whether these nerves compete like other systems in the body, where those with stronger connections punish the weaker ones,” says Ginty. The team turned their attention to other genes they found to be NGF dependent; two of which code for proteins that kill neighboring nerve cells and another is the receptor for these death proteins.
According to Ginty, nerves that connect to muscles undergo a similar process called synapse elimination where stronger connections stay connected and weaker ones are eliminated. The team wondered if this is also true of peripheral nerve cells competing for NGF availability and ultimate cell survival. To test this idea they plugged these three additional genes into their computer model, assuming that the stronger connected nerve cell punishes its neighbors by releasing the two proteins capable of killing. The computer model showed again, that half the nerve cells die over time, but this time the death occurred over two to three days rather than 100 days, just as in living animals.
To confirm that the model is accurate, the team went back to genetically altered mice. They predicted that removal of the punishment signals should delay cell death as observed in their early computer simulations. Indeed, nerve cells in mice lacking the receptor protein for the death signals died much slower than in mice with the receptor protein intact.
“I never would have believed that these three genes could speed up competition so much,” says Ginty. “But there it was in front of us-it was amazing.”
The research was funded by the National Institutes of Health, a Woodrow Wilson Undergraduate Research Fellowship, and the Howard Hughes Medical Institute.
Authors on the paper are Christopher Deppmann, Stefan Mihalas, Nikhil Sharma, Bonnie Lonze, Ernst Niebur and Ginty, all of Hopkins.
Johns Hopkins Scientists Reveal New Survival Mechanism for Neurons