Featured Research

from universities, journals, and other organizations

Killer Competition: Neurons Duke It Out For Survival

Date:
May 8, 2008
Source:
Johns Hopkins Medical Institutions
Summary:
The developing nervous system makes far more nerve cells than are needed to ensure target organs and tissues are properly connected to the nervous system. As nerves connect to target organs, they somehow compete with each other resulting in some living and some dying. Now, using a combination of computer modeling and molecular biology, neuroscientists have discovered how the target tissue helps newly connected peripheral nerve cells strengthen their connections and kill neighboring nerves.

The developing nervous system makes far more nerve cells than are needed to ensure target organs and tissues are properly connected to the nervous system. As nerves connect to target organs, they somehow compete with each other resulting in some living and some dying. Now, using a combination of computer modeling and molecular biology, neuroscientists at Johns Hopkins have discovered how the target tissue helps newly connected peripheral nerve cells strengthen their connections and kill neighboring nerves. The study was published in the April 18th issue of Science.

"It was hard to imagine how this competition happens because the signal that leads cells to their targets also is responsible for keeping them alive, which begs the question: How do half of them die?" says David Ginty, Ph.D., a professor of neuroscience and investigator of the Howard Hughes Medical Institute.

Target tissues innervated by so-called peripheral neurons coax nerves to grow toward them by releasing nerve growth factor protein, or NGF. Once the nerve reaches its target, NGF changes from a growth cue to a survival factor. In fact, when some populations of nerve cells are deprived of NGF they die. To further investigate how this NGF-dependent survival effect works the researchers looked for genes that are turned on by NGF in developing nerve cells.

They found hundreds of genes that respond to NGF genes, some of which are involved in enhancing NGF's effect. With the observation that NGF seems to control genes that improve NGF effectiveness, Ginty's team hypothesized that this could be the way in which nerve cells compete with one another for survival. To test this idea the team turned to colleagues at the Mind/Brain Institute at Hopkins who specialize in computer modeling of such problems.

The computer model they built assigns each nerve cell its own mathematical equation that take into account how much NGF the cell encounters 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.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Journal Reference:

  1. C. D. Deppmann, S. Mihalas, N. Sharma, B. E. Lonze, E. Niebur, D. D. Ginty. A Model for Neuronal Competition During Development. Science, 2008; 320 (5874): 369 DOI: 10.1126/science.1152677

Cite This Page:

Johns Hopkins Medical Institutions. "Killer Competition: Neurons Duke It Out For Survival." ScienceDaily. ScienceDaily, 8 May 2008. <www.sciencedaily.com/releases/2008/05/080506165527.htm>.
Johns Hopkins Medical Institutions. (2008, May 8). Killer Competition: Neurons Duke It Out For Survival. ScienceDaily. Retrieved April 20, 2014 from www.sciencedaily.com/releases/2008/05/080506165527.htm
Johns Hopkins Medical Institutions. "Killer Competition: Neurons Duke It Out For Survival." ScienceDaily. www.sciencedaily.com/releases/2008/05/080506165527.htm (accessed April 20, 2014).

Share This



More Health & Medicine News

Sunday, April 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Nine-Month-Old Baby Can't Open His Mouth

Nine-Month-Old Baby Can't Open His Mouth

Newsy (Apr. 19, 2014) Nine-month-old Wyatt Scott was born with a rare disorder called congenital trismus, which prevents him from opening his mouth. Video provided by Newsy
Powered by NewsLook.com
'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins