Navigation Links
MDC researchers reveal molecular mechanism underlying severe anomalies of the forebrain

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.

Helmholtz Association of German Research Centres

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:
(Date:11/18/2015)...  As new scientific discoveries deepen our understanding of ... providers face challenges in better using that knowledge to ... as more children continue to survive pediatric cancer, that ... age. John M. Maris, M.D ., a ... (CHOP) . --> John M. Maris, ...
(Date:11/17/2015)... 2015  Vigilant Solutions announces today that Mr. ... Directors. --> --> ... the partnership at TPG Capital, one of the largest ... Billion in revenue.  He founded and led TPG,s Operating ... companies, from 1997 to 2013.  In his first role, ...
(Date:11/12/2015)... , Nov. 12, 2015  Arxspan has ... of MIT and Harvard for use of its ... information management tools. The partnership will support the ... biological and chemical research information internally and with ... be used for managing the Institute,s electronic laboratory ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... PHILADELPIA, PA (PRWEB) , ... November 24, 2015 , ... ... young entrepreneurs at competitive events in five states to develop and pitch their BIG ... student projects from each state are competing for votes to win the title of ...
(Date:11/24/2015)... November 24, 2015 SHPG ) announced today ... the Piper Jaffray 27 th Annual Healthcare Conference in ... 2015, at 8:30 a.m. EST (1:30 p.m. GMT). --> ... Officer, will participate in the Piper Jaffray 27 th Annual ... on Tuesday, December 1, 2015, at 8:30 a.m. EST (1:30 p.m. ...
(Date:11/24/2015)... , Nov. 24, 2015  Tikcro Technologies Ltd. (OTCQB: TIKRF) today announced ... 29, 2015 at 11:00 a.m. Israel time, at ... 98 Yigal Allon Street, 36 th Floor, Tel Aviv, ... Eric Paneth and Izhak Tamir to the Board of ... as external directors; , approval of an amendment to certain terms ...
(Date:11/24/2015)... SAN FRANCISCO , Nov. 24, 2015 /PRNewswire/ ... today announced that Emily Leproust, Ph.D., Twist Bioscience ... Piper Jaffray Healthcare Conference on December 1, 2015 ... Palace Hotel in New York City. ... . Twist Bioscience is on ...
Breaking Biology Technology: