Navigation Links
MDC researchers reveal molecular mechanism underlying severe anomalies of the forebrain
Date:2/14/2012

Researchers of the Max Delbrck 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 (Developmental Cell, DOI 10.1016/j.devcel.2011.11.023)*.

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.


'/>"/>
Contact: bachtler@mdc-berlin.de
bachtler@mdc-berlin.de
49-309-406-3896
Helmholtz Association of German Research Centres
Source:Eurekalert

Related biology news :

1. NC State researchers get to root of parasite genome
2. Researchers find animal with ability to survive climate change
3. Researchers find an essential gene for forming ears of corn
4. Researchers note differences between people and animals on calorie restriction
5. Researchers study acoustic communication in deep-sea fish
6. Researchers discover that growing up too fast may mean dying young in honey bees
7. Researchers study how pistachios may improve heart health
8. UI researchers find potentially toxic substance present in Chicago air
9. Researchers develop new self-training gene prediction program for fungi
10. Case Western Reserve University researchers track Chernobyl fallout
11. Childrens National researchers develop novel anti-tumor vaccine
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/20/2016)... , June 20, 2016 Securus ... justice technology solutions for public safety, investigation, corrections ... the prisons involved, it has secured the final ... (DOC) facilities for Managed Access Systems (MAS) installed. ... additional facilities to be installed by October, 2016. ...
(Date:6/7/2016)... June 7, 2016  Syngrafii Inc. and San ... relationship that includes integrating Syngrafii,s patented LongPen™ eSignature ... This collaboration will result in greater convenience for ... union, while maintaining existing document workflow and compliance ... ...
(Date:6/1/2016)... , June 1, 2016 Favorable ... Election Administration and Criminal Identification to Boost Global Biometrics ... recently released TechSci Research report, " Global Biometrics Market ... Competition Forecast and Opportunities, 2011 - 2021", the global ... by 2021, on account of growing security concerns across ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... , June 23, 2016   Boston Biomedical ... novel compounds designed to target cancer stemness pathways, ... been granted Orphan Drug Designation from the U.S. ... of gastric cancer, including gastroesophageal junction (GEJ) cancer. ... designed to inhibit cancer stemness pathways by targeting ...
(Date:6/23/2016)... 2016  The Prostate Cancer Foundation (PCF) is pleased to announce ... cures for prostate cancer. Members of the Class of 2016 were selected from ... Read More About the Class of 2016 PCF Young Investigators ... ... ...
(Date:6/23/2016)... Durham, NC (PRWEB) , ... June 23, 2016 , ... ... Odense University Hospital in Denmark detail how a patient who developed lymphedema after being ... (fat) tissue. The results could change the paradigm for dealing with this debilitating, frequent ...
(Date:6/23/2016)... ... 23, 2016 , ... ClinCapture, the only free validated electronic ... showcase its product’s latest features from June 26 to June 30, 2016 for ... Disrupting Clinical Trials in The Cloud during the conference. DIA (Drug Information ...
Breaking Biology Technology: