The AP-1 transcription factor component Fosl2 potentiates the rate of myocardial differentiation from the zebrafish second heart field

Abstract

The vertebrate heart forms through successive phases of cardiomyocyte differentiation. Initially, cardiomyocytes derived from first heart field (FHF) progenitors assemble the linear heart tube. Thereafter, second heart field (SHF) progenitors differentiate into cardiomyocytes that are accreted to the poles of the heart tube over a well-defined developmental window. Although heart tube elongation deficiencies lead to life-threatening congenital heart defects, the variables controlling the initiation, rate and duration of myocardial accretion remain obscure. Here, we demonstrate that the AP-1 transcription factor, Fos-like antigen 2 (Fosl2), potentiates the rate of myocardial accretion from the zebrafish SHF. fosl2 mutants initiate accretion appropriately, but cardiomyocyte production is sluggish, resulting in a ventricular deficit coupled with an accumulation of SHF progenitors. Surprisingly, mutant embryos eventually correct the myocardial deficit by extending the accretion window. Overexpression of Fosl2 also compromises production of SHFderived ventricular cardiomyocytes, a phenotype that is consistent with precocious depletion of the progenitor pool. Our data implicate Fosl2 in promoting the progenitor to cardiomyocyte transition and uncover the existence of regulatory mechanisms to ensure appropriate SHF-mediated cardiomyocyte contribution irrespective of embryonic stage.

Genome-Wide Temporal Profiling of Transcriptome and Open Chromatin of Early Cardiomyocyte Differentiation Derived From hiPSCs and hESCs

“…55, 58 Complex of JUN and FOS proteins are known to form the subunits of Activator protein 1 (AP-1), which is a transcription factor and required for cardiac differentiation. 59, 60 MEIS2 was also found to act as a critical TF for regulation of cardiomyocyte differentiation derived from H7-hESC line. 7 In addition, some TFs showed correlation between WGCNA and motif enrichments, while they were had low weighted-connectivity or showed variability in occurrence of motif-enrichment among cell lines, they included RXRA and MGA (module 8), RXRG, GATA3 and GATA6 (module 2), EBF1, GATA2 and GATA 5 (module 1) (Figure 7B).…”

MicroRNA-155-5p suppresses cardiomyocytes apoptosis induced by hypoxia/reoxygenation via targeting fos-related antigen 2

“…The phosphorylation of FRA2 increases itself DNA binding activity. Consistent with FRA1, the FRA2 lacks C-terminal trans-activating domain [17]. Previous study indicates that FRA-2 mediates oxygen-sensitive induction of transforming growth factor-β (TGF-β) in cardiac fibroblasts [18].…”

An alternatively spliced zebrafishjnk1atranscript has an essential and non-redundant role in development of the first heart field derived proximal ventricular chamber

“…It is possible to imagine that some cells may become lost during migration, and in isolation undergo cell death or differentiate into other tissues. Other studies demonstrating perturbance in FHF/SHF complements [24, 37] have similarly not identified where or how cells are lost.…”

“…It has been suggested that in certain cell types, Jnk may activate AP1 and related factors [38]. In zebrafish it has been shown that AP1 disturbance affects only the SHF ventricular cardiomyocyte addition [37]. Hence jnk1a is unlikely to be acting through AP1 in this FHF context.…”