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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 Monstruosités humaines, ouvrage contenant une classification des monstres ... Paris, 1822), working in the Musée National d'Histoire 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 generate the various structures of the face through the activation of Dlx patterning genes.

The most intriguing observation of this study is that the morphological characters obtained when treating embryos at slightly different developmental times resemble closely anatomical features found in other species. For example the authors describe the progressive transformation of ossicles of the middle ear into components of the jaw apparatus. Furthermore, the treated skulls display combinations of characters present in non-mammalian species arranged in a temporal sequence strongly reminiscent of the evolutionary sequence of gnathostomal jaws. They conclude with the hypothesis that modulation of a common regulatory signalling mechanism could be at the origin of changes in jaw structures between species.

The implications of these findings go much beyond the original scope of this study and will have a major impact on developmental biology and evolutionary biology as they pave a way to understand the complexity of the dynamic patterning events at the origin of face development and evolution.



The following press release refers to an upcoming article in PLoS ONE. The release has been provided by the article authors and/or their institutions. Any opinions expressed in this are the personal views of the contributors, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the release and article and your use of such information.

Giovanni LEVI
Tel: +33-1-40793621
Centre National de La Recherche Scientifique - UMR5166
Museum National d'Histoire Naturelle

Citation: Vieux-Rochas M, Coen L, Sato T, Kurihara Y, Gitton Y, et al (2007) Molecular Dynamics of Retinoic Acid-Induced Craniofacial Malformations: Implications for the Origin of Gnathostome Jaws. PLoS ONE 2(6): e510. doi:10.1371/journal.pone.0000510



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