Featured Research

from universities, journals, and other organizations

Fragile X syndrome gene's role in shaping brain uncovered

Date:
May 9, 2010
Source:
UT Southwestern Medical Center
Summary:
Researchers have discovered how the genetic mutation that causes Fragile X syndrome, the most common form of inherited mental retardation, interferes with the "pruning" of nerve connections in the brain.

Researchers at UT Southwestern Medical Center have discovered how the genetic mutation that causes Fragile X syndrome, the most common form of inherited mental retardation, interferes with the "pruning" of nerve connections in the brain. Their findings appear in the April 29 issue of Neuron.

Related Articles


Soon after birth, the still-developing brain of a mammal produces too many nerve connections that create "noise" in the nervous system. The brain finds it hard to process these signals, like a person trying to have a conversation at a loud party. But as the brain matures and learning takes place, some nerve connections naturally become stronger while others weaken and die, leading to an adult with a properly wired brain.

Fragile X is caused by a mutation in a single gene, Fmr1, on the X chromosome. The gene codes for a protein called FMRP, which plays a role in learning and memory but whose full function is unknown. The protein's role in pruning nerve connections had been unclear.

"I think we've uncovered a core function for the gene involved in this disease, and if we can find other biochemical methods involved in nerve pruning, we might be able to help correct this," said Dr. Kimberly Huber, associate professor of neuroscience at UT Southwestern and senior author of the study.

In the current study, Dr. Huber and her colleagues examined nerve cells isolated from mice that had been engineered to lack the Fmr1 gene and, therefore, did not produce FMRP protein. They then tested whether the lack of FMRP affected the functions of another protein called MEF2, which is known to be involved in pruning nerve connections.

The researchers found that nerve cells lacking FMRP were unable to respond to MEF2. Adding FMRP to the cells restored MEF2's normal function.

"We were massively activating the MEF2 gene in the cell, and it did absolutely nothing without FMRP," Dr. Huber said. Such an all-or-nothing requirement in a biochemical relationship is rare, she said.

The findings also raise questions about how the two proteins interact physically. MEF2 works in the nucleus of a cell, where it controls whether other genes are turned on or off. FMRP shuttles in and out of the cell's nucleus and into its main body.

"This opens up new ideas about how processes in the cell's nucleus, near its DNA, can affect the nerve connections, which are very far away at the other end of the cell," Dr. Huber said. "We think MEF2 is making messenger RNA [ribonucleic acid], which translates the genetic code of the DNA, and FMRP is binding to the RNA and either transporting it to the nerve connections and/or controlling how the RNA makes protein."

Further research will focus on the relationship between the proteins. For instance, one might directly control the other, or they might work together on a common target, Dr. Huber said.

"This work might not have clinical implications for quite a while," she said. "The goal for us as scientists is to understand how these genes relate to mechanisms that control the development of nerve connections."

Like other genetic diseases carried on the X chromosome, Fragile X syndrome strikes boys more often and more severely than girls. Girls have two X chromosomes, so a normal gene on one chromosome can mitigate the effects of the disease if the gene on the other X chromosome is abnormal. Boys, however, have only one X chromosome, so if they inherit an abnormal gene on the X chromosome, they have no protection.

Other UT Southwestern researchers involved in the study were lead author and former graduate student Brad Pfeiffer; Dr. Tong Zang, postdoctoral researcher in neuroscience; Dr. Julia Wilkerson, postdoctoral researcher in neuroscience; Dr. Makoto Taniguchi, postdoctoral researcher in psychiatry; Marina Maksimova, research assistant in neuroscience; Dr. Laura Smith, postdoctoral researcher in psychiatry; and Dr. Christopher Cowan, assistant professor of psychiatry.

The study was funded by the National Institutes of Health, Autism Speaks, the Whitehall Foundation and Simons Foundation.


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Brad E. Pfeiffer, Tong Zang, Julia R. Wilkerson, Makoto Taniguchi, Marina A. Maksimova, Laura N. Smith, Christopher W. Cowan, Kimberly M. Huber. Fragile X Mental Retardation Protein Is Required for Synapse Elimination by the Activity-Dependent Transcription Factor MEF2. Neuron, 2010; 66 (2): 191 DOI: 10.1016/j.neuron.2010.03.017

Cite This Page:

UT Southwestern Medical Center. "Fragile X syndrome gene's role in shaping brain uncovered." ScienceDaily. ScienceDaily, 9 May 2010. <www.sciencedaily.com/releases/2010/05/100507161419.htm>.
UT Southwestern Medical Center. (2010, May 9). Fragile X syndrome gene's role in shaping brain uncovered. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2010/05/100507161419.htm
UT Southwestern Medical Center. "Fragile X syndrome gene's role in shaping brain uncovered." ScienceDaily. www.sciencedaily.com/releases/2010/05/100507161419.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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