Molecular dynamics of retinoic acid-induced craniofacial malformations: implications for the origin of gnathostome jaws. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue PLoS ONE Année : 2007

Molecular dynamics of retinoic acid-induced craniofacial malformations: implications for the origin of gnathostome jaws.

Takahiro Sato
  • Fonction : Auteur
Yukiko Kurihara
  • Fonction : Auteur
Yorick Gitton
Ottavia Barbieri
  • Fonction : Auteur
Karine Le Blay
  • Fonction : Auteur
  • PersonId : 1270778
Giorgio R. Merlo
  • Fonction : Auteur
Marc Ekker
  • Fonction : Auteur
Hiroki Kurihara
  • Fonction : Auteur
Philippe Janvier
  • Fonction : Auteur
Giovanni Levi

Résumé

BACKGROUND: Intake of retinoic acid (RA) or of its precursor, vitamin A, during early pregnancy is associated with increased incidence of craniofacial lesions. The origin of these teratogenic effects remains enigmatic as in cranial neural crest cells (CNCCs), which largely contribute to craniofacial structures, the RA-transduction pathway is not active. Recent results suggest that RA could act on the endoderm of the first pharyngeal arch (1stPA), through a RARbeta-dependent mechanism. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that RA provokes dramatically different craniofacial malformations when administered at slightly different developmental times within a narrow temporal interval corresponding to the colonization of the 1(st) PA by CNCCs. We provide evidence showing that RA acts on the signalling epithelium of the 1(st) PA, gradually reducing the expression of endothelin-1 and Fgf8. These two molecular signals are instrumental in activating Dlx genes in incoming CNCCs, thereby triggering the morphogenetic programs, which specify different jaw elements. CONCLUSIONS/SIGNIFICANCE: The anatomical series induced by RA-treatments at different developmental times parallels, at least in some instances, the supposed origin of modern jaws (e.g., the fate of the incus). Our results might provide a conceptual framework for the rise of jaw morphotypes characteristic of gnathostomes.

Dates et versions

hal-00180105 , version 1 (17-10-2007)

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Citer

Maxence Vieux-Rochas, Laurent Coen, Takahiro Sato, Yukiko Kurihara, Yorick Gitton, et al.. Molecular dynamics of retinoic acid-induced craniofacial malformations: implications for the origin of gnathostome jaws.. PLoS ONE, 2007, 2 (6), pp.e510. ⟨10.1371/journal.pone.0000510⟩. ⟨hal-00180105⟩

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