Timeline of Developmental Defects Generated upon Genetic Inhibition of the Retinoic Acid Receptor Signaling Pathway.
Fiche publication
Date publication
janvier 2023
Journal
Biomedicines
Auteurs
Membres identifiés du Cancéropôle Est :
Dr HERAULT Yann, Dr TELETIN Marius, Dr MARK Manuel
Tous les auteurs :
Teletin M, Mark M, Wendling O, Vernet N, Féret B, Klopfenstein M, Herault Y, Ghyselinck NB
Lien Pubmed
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- retinoic acid (ATRA) synthesising enzymes establishes that cardiac looping is the earliest known morphogenetic event requiring a functional ATRA-activated RAR signalling pathway.
Mots clés
HREM, axial rotation, cardiac looping, embryonic turning, eye development, heart development, inner ear development, lung development, mouse
Référence
Biomedicines. 2023 01 12;11(1):