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Evolutionary relevance of retinoic acid-induced craniofacial malformations

In the 19th century the works of Etienne Geoffroy Saint-Hilaire and of his son Isidore (e.g. Philosophie anatomique. Des Monstruosits humaines, ouvrage contenant une classification des monstres Paris, 1822), working in the Muse National dHistoire Naturelle in Paris, were fundamental in demonstrating, through comparative anatomical studies, that a cause of monstrosity was to be ascribed to abnormal development of the foetus.

These findings put an end to the conception that a pregnant woman could, through her imagination, cause the development of foetal defects. With the manuscript Molecular dynamics of retinoic acid-induced craniofacial malformations: implications for the origin of gnathostome jaws to appear in the June 6th issue of the online, open-access journal PLoS ONE, the group of Dr. Giovanni Levi, working in the CNRS UMR5166 in the same institution as Geoffroy Saint-Hilaire and collaborating with the paleontologist Philippe Janvier, revisits some of these concepts from the modern view of molecular genetics.

They start from the observation that intake of high doses of vitamin A or of its derivative, retinoic acid (RA), during early pregnancy is known to increase dramatically the risk of severe craniofacial malformations to the developing foetus. How these developmental lesions are generated remains, however, enigmatic since neural crest cells, which generate most craniofacial structures, do not respond to RA.

The authors perform a detailed anatomical analysis of the craniofacial defects induced by treating mouse embryos with RA at precise developmental times within a short temporal interval corresponding to the 3rd to 5th week of human foetal development. The defects induced are profoundly different depending upon the exact moment at which RA is administered.

The authors show that these defects are associated with the progressive down-regulation of molecular signals involved in instructing neural crest cells to gen
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Contact: Giovanni Levi
glevi@mnhn.fr
33-140-793-621
Public Library of Science
5-Jun-2007


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