The Role of Bmp- and Fgf Signaling Modulating Mouse Proepicardium Cell Fate.

Carlos Garcia-Padilla,Maria Del Mar Muñoz-Gallardo,Diego Franco,Lledó Palencia-Vincent,Amelia Aranega,Isabel S Garcia-Valencia,Francisco Hernandez-Torres,Angel Dueñas,Estefania Lozano-Velasco

doi:10.3389/fcell.2021.757781

Carlos Garcia-Padilla, Maria Del Mar Muñoz-Gallardo + Show 7 more

Open Access

https://doi.org/10.3389/fcell.2021.757781

Copy DOI

Abstract

Bmp and Fgf signaling are widely involved in multiple aspects of embryonic development. More recently non coding RNAs, such as microRNAs have also been reported to play essential roles during embryonic development. We have previously demonstrated that microRNAs, i.e., miR-130, play an essential role modulating Bmp and Fgf signaling during early stages of cardiomyogenesis. More recently, we have also demonstrated that microRNAs are capable of modulating cell fate decision during proepicardial/septum transversum (PE/ST) development, since over-expression of miR-23 blocked while miR-125, miR-146, miR-223 and miR-195 enhanced PE/ST-derived cardiomyogenesis, respectively. Importantly, regulation of these microRNAs is distinct modulated by Bmp2 and Fgf2 administration in chicken. In this study, we aim to dissect the functional role of Bmp and Fgf signaling during mouse PE/ST development, their implication regulating post-transcriptional modulators such as microRNAs and their impact on lineage determination. Mouse PE/ST explants and epicardial/endocardial cell cultures were distinctly administrated Bmp and Fgf family members. qPCR analyses of distinct microRNAs, cardiomyogenic, fibrogenic differentiation markers as well as key elements directly epithelial to mesenchymal transition were evaluated. Our data demonstrate that neither Bmp2/Bmp4 nor Fgf2/Fgf8 signaling is capable of inducing cardiomyogenesis, fibrogenesis or inducing EMT in mouse PE/ST explants, yet deregulation of several microRNAs is observed, in contrast to previous findings in chicken PE/ST. RNAseq analyses in mouse PE/ST and embryonic epicardium identified novel Bmp and Fgf family members that might be involved in such cell fate differences, however, their implication on EMT induction and cardiomyogenic and/or fibrogenic differentiation is limited. Thus our data support the notion of species-specific differences regulating PE/ST cardiomyogenic lineage commitment.

Highlights

Bmp and Fgf signaling are widely involved in multiple aspects of embryonic development (Ornitz and Itoh, 2015; Ornitz and Marie, 2015; Wu et al, 2016; Graf et al, 2016; Salazar et al, 2016; Zinski et al, 2018; Xie et al, 2020; MossahebiMohammadi et al, 2020)
We have previously reported that Bmp and Fgf family members, can distinctly modulate the expression of microRNAs that can differently modulate proepicardial/septum transversum (PE/ST)-derived cardiomyogenesis
These data demonstrate that distinct Bmp and Fgf family members can differentially modulate those microRNAs that significantly enhanced cardiomyogenesis, those that mildly enhanced it and those that do not enhance or even inhibit it

Summary

Introduction

Bmp and Fgf signaling are widely involved in multiple aspects of embryonic development (Ornitz and Itoh, 2015; Ornitz and Marie, 2015; Wu et al, 2016; Graf et al, 2016; Salazar et al, 2016; Zinski et al, 2018; Xie et al, 2020; MossahebiMohammadi et al, 2020). The role of Bmp and Fgf has been reported during the formation of the proepicardium/septum transversum (PE/ST) (Torlopp et al, 2010), providing signaling cues to direct the pericardial mesoderm to either proepicardial or myocardial fate (Kruithof et al, 2006; van Wijk et al, 2009). In this context, Bmp stimulates cardiomyocyte formation while Fgf stimulates epicardial differentiation in chicken embryos. MiR-195 is distinctly modulated by Bmp and Fgf signaling, supporting a role of this microRNA in the Bmpand Fgf-directed PE cell specification (Dueñas et al, 2020)

Objectives

Methods

Results

Conclusion