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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 16, 2012--------News Archive Return to: News Alerts

Cholesterol is vital for an embryo because it controls the development of the central nervous system. The lack of cholesterol can lead to severe disorders of the forebrain (prosencephalon), the largest region of the human brain.

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What Creates Forebrain Errors in Development

One in 250 pregnancies does not come to term because of holoprosencephaly (HPE). One in 16,000 children born with HPE suffer the mildest form as cleft lip and palate. Severe forms of HPE do not survive the first weeks of life.

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. In holoprosencephaly (HPE), the forebrain (prosencephalon) is incompletely formed. A receptor for cholesterol plays a key role in this outcome. If the receptor 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 can create vascular calcification in adults (atherosclerosis) which can lead 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 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 16,000 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 can be due to genetic factors, but environmental factors such as viral infections or alcohol abuse during pregnancy can also cause the malformation. Moreover, cholesterol metabolism is frequently disturbed in patients suffering HPE. Patients whose bodies cannot produce cholesterol due to a genetic disorder inevitably have HPE.

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 not completely understood. This study by the Berlin researchers gives a possible clue. They have identified a receptor called LRP2 which is formed in the neural tube and can bind lipoproteins, which are the transport form of cholesterol.

Interestingly, the LRP2 receptor also binds to an important signal molecule in forebrain development, sonic hedgehog (SHH). The researchers demonstrated that the lipoprotein receptor drives the accumulation of SHH in the neural tube at a specific site, inducing the development of the forebrain.

They also 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

Institutes contributing to this work: Max Delbrück Center for Molecular Medicine, and the Institute for Vegetative Anatomy Charité Universitätsmedizin, D-13125 Berlin, Germany.

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