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 Monstruosites humaines,
ouvrage contenant une classification des monstres ... Paris, 1822), working in the Musee 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.



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

plosone/doi/pone.0000510

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