A spatiotemporal gradient of mesoderm assembly governs cell fate and morphogenesis of the early mammalian heart

Abstract

AbstractUsing four-dimensional whole-embryo light sheet imaging with improved and accessible computational tools, we longitudinally reconstruct early murine cardiac development at single-cell resolution. Nascent mesoderm progenitors form opposing density and motility gradients, converting the temporal birth sequence of gastrulation into a spatial anterolateral-to-posteromedial arrangement. Migrating precardiac mesoderm doesn’t strictly preserve cellular neighbor relationships; spatial patterns only become solidified as the cardiac crescent emerges. Progenitors undergo a heretofore unknown mesenchymal-to-epithelial transition, with a first heart field (FHF) ridge apposing a motile juxtacardiac field (JCF). Anchored along the ridge, the FHF epithelium rotates the JCF forward due to push-pull morphodynamics of the second heart field, which forms the nascent heart tube. In Mesp1 mutants that fail to make a cardiac crescent, mesoderm remains highly motile but directionally incoherent, resulting in density gradient inversion. Our practicable live embryo imaging approach defines spatial origins and behaviors of cardiac progenitors, and identifies their unanticipated morphological transitions.