Featured Research

from universities, journals, and other organizations

Molecular mechanism underlying severe anomalies of the forebrain

Date:
February 14, 2012
Source:
Helmholtz Association of German Research Centres
Summary:
Researchers have identified a molecular mechanism underlying the most common malformation of the brain in humans. In holoprosencephaly, the forebrain is only incompletely formed. Here a binding site (receptor) for cholesterol plays a key role. If this receptor is defective, specific signals cannot be received, and the forebrain cannot separate into two hemispheres, as the researchers have now shown in mice.

Researchers of the Max Delbrόck Center for Molecular Medicine (MDC) Berlin-Buch have now identified and described a molecular mechanism underlying the most common malformation of the brain in humans. In holoprosencephaly (HPE), the forebrain (prosencephalon) is only incompletely formed. Here a binding site (receptor) for cholesterol plays a key role. If this receptor is defective, specific signals cannot be received, and the forebrain cannot separate into two hemispheres, as Dr. Annabel Christ, Professor Thomas Willnow and Dr. Annette Hammes have now shown in mice.

Cholesterol has a bad reputation because it may lead to vascular calcification in adults (atherosclerosis) as well as to heart attacks and strokes. However, cholesterol is vital for embryonic development because it controls the development of the central nervous system. The lack of it can lead to severe developmental disorders of the forebrain (prosencephalon), the largest region of the human brain. One in 250 pregnancies does not come to term due to this malformation called holoprosencephaly (HPE). One in 16000 children is born with HPE, of which the mildest form is cleft lip and palate. In severe forms of HPE the affected children do not survive the first weeks of life.

HPE may be due to genetic factors, but environmental factors such as viral infections or alcohol abuse during pregnancy may also cause the malformation. Moreover, the cholesterol metabolism is also frequently disturbed. Thus, patients whose bodies cannot produce cholesterol due to a genetic disorder inevitably have HPE.

As Professor Willnow explained, the human brain develops from the neural tube, a simple tube-like cluster of cells in the embryo. Why defects in cholesterol metabolism lead to a developmental disorder of the neural tube and to HPE is thus far not completely understood. The studies of the Berlin researchers may give a possible clue. They identified a receptor called LRP2 that is formed in the neural tube and can bind lipoproteins, which are the transport form of cholesterol.

Interestingly, this receptor also binds an important signal molecule of forebrain development (sonic hedgehog, abbreviated SHH). As the researchers demonstrated, this lipoprotein receptor drives the accumulation of SHH in the neural tube at a specific site and induces the development of the forebrain structures. The researchers now suspect that cholesterol -- directly or indirectly -- plays a central role in controlling the activity of this novel receptor and assume that disturbances in cholesterol metabolism lead to a loss of function of this auxiliary receptor for SHH signaling.


Story Source:

The above story is based on materials provided by Helmholtz Association of German Research Centres. Note: Materials may be edited for content and length.


Journal Reference:

  1. Annabel Christ, Anna Christa, Esther Kur, Oleg Lioubinski, Sebastian Bachmann, Thomas E. Willnow, Annette Hammes. LRP2 Is an Auxiliary SHH Receptor Required to Condition the Forebrain Ventral Midline for Inductive Signals. Developmental Cell, 2012; 22 (2): 268 DOI: 10.1016/j.devcel.2011.11.023

Cite This Page:

Helmholtz Association of German Research Centres. "Molecular mechanism underlying severe anomalies of the forebrain." ScienceDaily. ScienceDaily, 14 February 2012. <www.sciencedaily.com/releases/2012/02/120214121850.htm>.
Helmholtz Association of German Research Centres. (2012, February 14). Molecular mechanism underlying severe anomalies of the forebrain. ScienceDaily. Retrieved August 22, 2014 from www.sciencedaily.com/releases/2012/02/120214121850.htm
Helmholtz Association of German Research Centres. "Molecular mechanism underlying severe anomalies of the forebrain." ScienceDaily. www.sciencedaily.com/releases/2012/02/120214121850.htm (accessed August 22, 2014).

Share This




More Health & Medicine News

Friday, August 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) — An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) — Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) — It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. Video provided by Newsy
Powered by NewsLook.com
Lost Brain Cells To Blame For Sleep Problems Among Seniors

Lost Brain Cells To Blame For Sleep Problems Among Seniors

Newsy (Aug. 21, 2014) — According to a new study, elderly people might have trouble sleeping because of the loss of a certain group of neurons in the brain. 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