Featured Research

from universities, journals, and other organizations

UCSD Researchers Demonstrate Protein Role Required For Normal Brain Development

Date:
June 9, 2003
Source:
University Of California - San Diego
Summary:
An essential step in understanding how the brain develops and related brain disorders that occur when the movement of neurons is defective, has been announced by researchers at the University of California, San Diego (UCSD) School of Medicine in the July 2003 print edition of the journal Nature Genetics.

An essential step in understanding how the brain develops and related brain disorders that occur when the movement of neurons is defective, has been announced by researchers at the University of California, San Diego (UCSD) School of Medicine in the July 2003 print edition of the journal Nature Genetics. The study is published online by the Nature website on June 8. The researchers found that normal brain development requires 14-3-3 epsilon, a member of a protein family universally found in everything from yeast to mammals. In studies with humans and mice, the researchers determined that death or severe brain abnormalities occurred when the protein was defective or missing.

"This is the first demonstration in mammals that 14-3-3 epsilon is essential for brain development," said the paper's senior author, Anthony Wynshaw-Boris, M.D., Ph.D., UCSD associate professor of pediatrics and medicine. "We also showed that the gene is always deleted on one chromosome in patients with a rare, but severe brain disorder called Miller-Dieker syndrome (MDS), a form of lissencephaly, which means "smooth brain".

In normal brain development, neurons migrate to various areas of the brain. Lissencephaly is a severe developmental defect of the brain caused when neurons born deep within the brain are unable to migrate normally to areas such as the hippocampus and cortex. In addition to smoothness of the brain surface, there is a thickening of the cortex, with four rather than six layers. Children with MDS, in addition to a severely damaged brain from lissencephaly, have characteristic facial features, such as a prominent forehead, short nose, and malformed ears and eyes. Patients with MDS have the severest form of a lissencephaly, which renders individuals with profound mental retardation, increasingly severe epilepsy and early death.

LIS1 (which stands for Lissencephaly-1) is a gene that is deleted or mutated on a chromosomal region of chromosome 17 (called 17p13.3) in many children with lissencephaly. LIS1 resides fairly close to the 14-3-3 epsilon gene on this chromosome. Patients with lissencephaly only have deletions of one copy of LIS1, but never 14-3-3 epsilon, while patients with MDS have deletions of both genes on the same chromosome.

One of the genes that directly interacts with LIS1 and is involved in that migration, called NUDEL, was discovered and named by the Wynshaw-Boris team, which published their findings December 20, 2000 in the journal Neuron. In new studies with mice lacking 14-3-3 epsilon, the Wynshaw-Boris teams determined that 14-3-3 epsilon binds to NUDEL, which may explain its essential role in neuronal migration.

Wynshaw-Boris explained that NUDEL becomes phosphorylated (combines with phosphoric acid or a phosphorus-containing group) by interaction with another molecular compound called Cdk5/p35. By binding to the phosphorylated form of NUDEL, 14-3-3 epsilon protects NUDEL from losing its phosphorylation through interactions with other molecules, thus stabilizing it for its role in neuronal migration.

"Not only does out study determine a novel function for 14-3-3 epsilon, but it also provides a molecular explanation for why MDS patients have more severe lissencephaly," Wynshaw-Boris said.

###The study was supported by grants from the National Institutes of Neurological Diseases and Stroke, an institutional grant from the Howard Hughes Medical Institute, and UCSD School of Medicine funds.

Additional authors were first author Kazuhito Toyo-oka, Ph.D., UCSD Departments of Pediatrics, Medicine and the UCSD Cancer Center; Aki Shionoya and Shinji Hirotsune, M.D., Ph.D. from Saitama Medical School PRESTO, and Japan Science and Technology Corporation; Michael J. Gambello, M.D., Ph.D., UCSD and the University of Texas Health Science Center, Houston; Carolos Cardoso, Ph.D., Richard Leventer, M.D., Heather L. Ward, William Dobyns, M.D., David Ledbetter, Ph.D., all from the University of Chicago; and Ramses Ayala and Li-Huei Tsai, Ph.D., Howard Hughes Medical Institute and Harvard Medical School.


Story Source:

The above story is based on materials provided by University Of California - San Diego. Note: Materials may be edited for content and length.


Cite This Page:

University Of California - San Diego. "UCSD Researchers Demonstrate Protein Role Required For Normal Brain Development." ScienceDaily. ScienceDaily, 9 June 2003. <www.sciencedaily.com/releases/2003/06/030609010457.htm>.
University Of California - San Diego. (2003, June 9). UCSD Researchers Demonstrate Protein Role Required For Normal Brain Development. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2003/06/030609010457.htm
University Of California - San Diego. "UCSD Researchers Demonstrate Protein Role Required For Normal Brain Development." ScienceDaily. www.sciencedaily.com/releases/2003/06/030609010457.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Possible Ebola Patient in Isolation at California Hospital

Possible Ebola Patient in Isolation at California Hospital

Reuters - US Online Video (Aug. 20, 2014) — A patient who may have been exposed to the Ebola virus is in isolation at the Kaiser Permanente South Sacramento Medical Center. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Raw: World's Oldest Man Lives in Japan

Raw: World's Oldest Man Lives in Japan

AP (Aug. 20, 2014) — A 111-year-old Japanese was certified as the world's oldest man by Guinness World Records on Wednesday. Sakari Momoi, a native of Fukushima in northern Japan, was given a certificate at a hospital in Tokyo. (Aug. 20) Video provided by AP
Powered by NewsLook.com
Do More Wedding Guests Make A Happier Marriage?

Do More Wedding Guests Make A Happier Marriage?

Newsy (Aug. 20, 2014) — A new study found couples who had at least 150 guests at their weddings were more likely to report being happy in their marriages. Video provided by Newsy
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) — Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 Video provided by AFP
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