Cholesterol and Brain Development
Holoprosencephaly (HPE) is the most common developmental forebrain anomaly in humans and is caused by the failure of the embryonic forebrain (the prosencephalon) to sufficiently divide into the two lobes of the cerebral hemispheres. The result is a single-lobed brain structure and severe skull and facial defects. About 1 in 250 pregnancies miscarries as a result of severe HPE. In less severe cases, about one in 16,000 babies is born with minor brain developmental and facial deformities that may affect the eyes, nose, and upper lip, such as median cleft lip and palate. HPE has several causes including prenatal viral infections or alcohol abuse during pregnancy. In many cases, a genetic defect in the metabolism of cholesterol results in HPE. Thus, some individuals with HPE are unable to produce cholesterol.
Now, scientists of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch in Germany have been able to show that a gene defect in one of the receptors for cholesterol, the receptor megalin, is responsible for severe damages of the forebrain and holopresencephaly in mice. Megalin is primarily produced by the embryonic tissue which later develops into the central nervous system. These results achieved by Robert Spoelgen, Dr. Annette Hammes, and Uwe Anzenberger of the research group of Professor Thomas Willnow have now been published online by the journal Development; http://dev.biologists.org/cgi/content/full/132/2/405; (January 2005, Vol. 132, Issue 2, pp. 405-414).*
*LRP2/megalin is required for patterning of the ventral telencephalon
Robert Spoelgen*, Annette Hammes*, Uwe Anzenberger*, Dietmar Zechner, Olav M. Andersen, Boris Jerchow and Thomas E. Willnow
Max-Delbrueck-Center for Molecular Medicine, Berlin, 13092, Germany
*Authors contributed equally
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