Cicarrelli, A. | bioRxiv Science

bioRxiv2023

Live-imaging reveals Coordinated Cell Migration and Cardiac Fate Determination during Mammalian Gastrulation.

Heart development involves the specification of cardiac progenitors at distinct stages and locations. Using live-imaging of mouse embryos between gastrulation and heart tube formation, we tracked individual mesodermal cells and reconstructed their lineage trees for up to five cell divisions. We found independent unipotent progenitors emerging at specific times, contributing exclusively to either left ventricle/atrioventricular canal (LV/AVC) or atrial myocytes. LV/AVC progenitors differentiated early to form the cardiac crescent, while atrial progenitors later generated the heart tubes inflow tract during morphogenesis. We also identified short-lived bipotent progenitors with broad potential, illustrating early developmental plasticity. Sister cells from bipotent progenitors displayed greater dispersion and more diverse migratory trajectories within the anterior mesoderm than those from unipotent progenitors. Bipotent progenitors contributing to extraembryonic mesoderm (ExEm) exhibited the fastest and most dispersed migrations, whereas those giving rise to endocardial, LV/AVC, and pericardial cells showed a more gradual divergence, with late-stage behavioural shifts: endocardial cells increased in speed, while pericardial cells slowed relative to LV/AVC cells. Together the data reveal the regulation of individual cell directionality and cardiac fate allocation within the seemingly unorganised migratory pattern of mesoderm cells.

developmental biology↗

bioRxiv2020

A FGF2-mediated incoherent feedforward loop inducesErk inhibition and promotes naive pluripotency

Naive pluripotency is a transient state during mammalian development that can be recapitulated indefinitely in vitro by inhibition of the mitogen-activated protein kinase (MAPK/Erk) signalling and activation of STAT and Wnt pathways. How Erk is inhibited in vivo to promote naive pluripotency remains largely unknown. By combining live cell imaging and quantitative proteomics we found that FGF2, a known Erk activator and pro-differentiation cue, induces instead long-term Erk inhibition in both ES cells and mouse embryos. We show that Erk inhibition results from a FGF2-induced incoherent feedforward loop. Importantly, we see that FGF2 induces up-regulation of naive pluripotency factors, down-regulation of DNA methylation by suppression of de novo DNA methylases thereby helping maintain naive pluripotency. We show that FGF2 is expressed maternally and propose that integration of signals from the embryos niche may contribute to the generation of embryonic lineages with the right cell proportions. We suggest that feedforward regulation may play a role driving transient, reversible developmental transitions.

developmental biology↗