ERK activity as a key player in determining cardiac cell fate choices

Abstract

Heart development is supported by diverse cell types originating from the lateral plate mesoderm (LPM), including the first heart field (FHF), the second heart field (SHF), which is a part of pharyngeal mesoderm, and the newly described juxta-cardiac field (JCF) that harbors progenitor cells of the epicardium. While FGF-MEK-ERK signalling has been implicated in various developmental mechanisms, its role in cardiac specification remains elusive. This signalling pathway involves autoinhibitory loops, acting at translational and post-translational levels, resulting in pulses of ERK activity. We hypothesized that this alternating ERK activity could direct binary cell fate choices during mesodermal specification. Using an in vitro system, we found that inhibition of ERK activity in the LPM, before cardiac commitment, resulted in enriched gene expression of JCF and pharyngeal mesoderm/SHF markers, with high proepicardial marker levels, at the expense of FHF-like cardiomyocyte markers. Our findings reveal a novel contribution of ERK signalling in cell differentiation within the cardiac lineages.