| Experiment Id | GSE199647 | Name | Torsion of the heart tube by shortage of progenitor cells: identification of Greb1l as a genetic determinant of criss-cross hearts in mice |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2024-05-03 |
| description | Despite their burden and impact, most congenital defects remain poorly understood by lack of knowledge of the embryological mechanisms. Here, we identify Greb1l mutants as the first mouse model of criss-cross 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 specific features of partial deficiency in retinoic acid signalling, suggesting that GREB1L is a novel modulator of this signalling. Spatio-temporal gene mapping and cross-correlated transcriptomic analyses further reveal the role of Greb1l in maintaining a pool of precursor cells during heart tube elongation, by controlling ribosome biogenesis and cell differentiation. Growth arrest and malposition of the outflow tract are predictive of abnormal tube remodelling in mutants. Our work on a rare cardiac malformation opens novel perspectives on the origin of a broader spectrum of congenital defects associated with GREB1L in humans. Transcriptomic analysis of the microdissected cardiac region at E8.5 of two Greb1l mutant mouse lines (G3 and G17), 4 mutants and 4 control littermates each. |
