Timeline of Developmental Defects Generated upon Genetic Inhibition of the Retinoic Acid Receptor Signaling Pathway - Archive ouverte HAL Access content directly
Journal Articles Biomedicines Year : 2023

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

Marius Teletin
  • Function : Author
Manuel Mark
  • Function : Author
  • PersonId : 1056874
Olivia Wendling
  • Function : Author
Nadège Vernet
Betty Féret
  • Function : Author
Muriel Klopfenstein
  • Function : Author
Yann Herault

Abstract

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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