Ségolène Bernheim, Adrien Borgel, Jean-François Le Garrec, Emeline Perthame, Audrey Desgrange, Cindy Michel, Laurent Guillemot, Sébastien Sart, Charles N Baroud, Wojciech Krezel, Francesca Raimondi, Damien Bonnet, Stéphane Zaffran, Lucile Houyel, Sigolène M Meilhac
Despite their burden, most congenital defects remain poorly understood, due to lack of knowledge of embryological mechanisms. Here, we identify Greb1l mutants as a mouse model of crisscross heart. Based on 3D quantifications of shape changes, we demonstrate that torsion of the atrioventricular canal occurs together with supero-inferior ventricles at E10.5, after heart looping. Mutants phenocopy partial deficiency in retinoic acid signaling, which reflect overlapping pathways in cardiac precursors. Spatiotemporal gene mapping and cross-correlated transcriptomic analyses further reveal the role of Greb1l in maintaining a pool of dorsal pericardial wall precursor cells during heart tube elongation, likely by controlling ribosome biogenesis and cell differentiation...
October 13, 2023: Developmental Cell