Timeline of Developmental Defects Generated upon Genetic Inhibition of the Retinoic Acid Receptor Signaling Pathway - Institut Génétique de Biologie Moléculaire et Cellulaire Accéder directement au contenu
Article Dans Une Revue Biomedicines Année : 2023

Timeline of Developmental Defects Generated upon Genetic Inhibition of the Retinoic Acid Receptor Signaling Pathway

Marius Teletin
  • Fonction : Auteur
Manuel Mark
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Olivia Wendling
  • Fonction : Auteur
Nadège Vernet
Betty Féret
  • Fonction : Auteur
Muriel Klopfenstein
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Yann Herault

Résumé

It has been established for almost 30 years that the retinoic acid receptor (RAR) signalling pathway plays essential roles in the morphogenesis of a large variety of organs and systems. Here, we used a temporally controlled genetic ablation procedure to precisely determine the time windows requiring RAR functions. Our results indicate that from E8.5 to E9.5, RAR functions are critical for the axial rotation of the embryo, the appearance of the sinus venosus, the modelling of blood vessels, and the formation of forelimb buds, lung buds, dorsal pancreatic bud, lens, and otocyst. They also reveal that E9.5 to E10.5 spans a critical developmental period during which the RARs are required for trachea formation, lung branching morphogenesis, patterning of great arteries derived from aortic arches, closure of the optic fissure, and growth of inner ear structures and of facial processes. Comparing the phenotypes of mutants lacking the 3 RARs with that of mutants deprived of all-trans retinoic acid (ATRA) synthesising enzymes establishes that cardiac looping is the earliest known morphogenetic event requiring a functional ATRA-activated RAR signalling pathway.
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hal-04021094 , version 1 (09-03-2023)

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Marius Teletin, Manuel Mark, Olivia Wendling, Nadège Vernet, Betty Féret, et al.. Timeline of Developmental Defects Generated upon Genetic Inhibition of the Retinoic Acid Receptor Signaling Pathway. Biomedicines, 2023, 11 (1), ⟨10.3390/biomedicines11010198⟩. ⟨hal-04021094⟩
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