GSE119124
RAR? is required for mesodermal gene expression prior to gastrulation
The developing vertebrate embryo is exquisitely sensitive to retinoic acid (RA) concentration, particularly during anteroposterior patterning. In contrast to Nodal and Wnt signaling, RA was not previously considered to be an instructive signal in mesoderm formation during gastrulation. Here we show that RAR? is indispensable for the expression of early mesoderm markers and is, therefore, an obligatory factor in mesodermal competence and/or maintenance. We identified several novel targets up-regulated by RAR signaling in the early gastrula that are expressed in the circumblastoporal ring and linked to mesodermal development. Despite overlapping expression patterns of the RA synthetic enzyme, Aldh1a2 and the RA- degrading enzyme, Cyp26a1, RAR?1 functions as a transcriptional activator in early mesoderm development, suggesting that RA ligand is available to the embryo earlier than previously appreciated. RAR?1 is required for cellular adhesion, as revealed by spontaneous dissociation and depletion of N-CAM mRNA in animal caps harvested from RAR?1 knockdown embryos. RAR?1 knockdown obliterates somite boundaries, and causes loss of MYOD protein in the presomitic mesoderm, but ectopic, persistent expression of MYOD protein in the trunk. Thus, RAR?1 is required for stabilizing the mesodermal fate, myogenic commitment, somite boundary formation, and terminal, skeletal muscle differentiation. Overall design: RNA-sequencing of gastrula stage embryos treated with RAR agonist TTNPB or RAR antagonist AGN193109