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Pregnancy Timeline by SemestersFemale Reproductive SystemFertilizationThe Appearance of SomitesFirst TrimesterSecond TrimesterThird TrimesterFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterDevelopmental Timeline
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February 27, 2012--------News Archive Return to: News Alerts

LRP2/megalin is required for patterning of the ventral telencephalon mmunohistology of coronal E10.5 forebrain sections indicate lack of expression of neuron-specific class III b-tubulin (TuJ1) in the ventral (arrowheads) but not in the dorsal telencephalon of megalin-/- compared to control embryos (+/+). (Photo reproduced from Development 132 (2) January 15, 2005: pp. 405-414. Copyright: The Company of Biologists Limited).

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Defective Cholesterol Receptor Behind Forebrain Errors in Development

In holoprosencephaly (HPE), the forebrain (prosencephalon) is incompletely formed, and a receptor for cholesterol plays a key role

Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch have identified a molecular mechanism underlying the most common malformation of the brain in humans.

If a receptor for cholesterol is defective, specific signals cannot be received, and the forebrain will not separate into two hemispheres. Dr. Annabel Christ, Professor Thomas Willnow and Dr. Annette Hammes have published their findings in Developmental Cell. (DOI 10.1016/j.devcel.2011.11.023)

Cholesterol has a bad reputation because it may lead to vascular calcification (atherosclerosis), heart attacks and strokes in adults.

However, cholesterol is vital for embryonic development because it controls the development of the central nervous system.

The lack of cholesterol 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, cholesterol metabolism is also frequently disturbed. Thus, patients whose bodies cannot produce cholesterol due to a genetic disorder inevitably have HPE.

As Professor Willnow explains, 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 Berlin researchers may have a possible clue, given they have 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.

*LRP2 Is an Auxiliary SHH Receptor Required to Condition the Forebrain Ventral Midline for Inductive Signals. Annabel Christ1, Anna Christa1, Esther Kur1, Oleg Lioubinski1, Sebastian Bachmann2, Thomas E. Willnow1,3* and Annette Hammes1,3

1Max Delbrück Center for Molecular Medicine

2Institute for Vegetative Anatomy Charité Universitätsmedizin, D-13125 Berlin, Germany

3These authors contributed equally to this work

Original article: http://www.eurekalert.org/pub_releases/2012-02/haog-mrr021412.php