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Updated: Oct 6, 2025
Epicardial Outgrowth Culture Assay and Ex Vivo Assessment of Epicardial-derived Cell Migration
Published on: March 18, 2016
The Role of Bmp- and Fgf Signaling Modulating Mouse Proepicardium Cell Fate
Carlos Garcia-Padilla1,2, Francisco Hernandez-Torres1,3,4, Estefania Lozano-Velasco1,3
1Cardiovascular Development Group, Department of Experimental Biology, University of Jaen, Jaen, Spain.
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.
Insights
This study reveals species-specific differences in embryonic development. Mouse proepicardial/septum transversum development does not respond to Bmp and Fgf signaling as seen in chickens, suggesting distinct regulatory mechanisms for cardiac lineage commitment.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Bone morphogenetic protein (Bmp) and Fibroblast growth factor (Fgf) signaling pathways are crucial for embryonic development.
- MicroRNAs (miRNAs) are non-coding RNAs that play essential roles in embryonic development, including modulating Bmp and Fgf signaling.
- Previous studies demonstrated miRNAs regulate cardiomyogenesis and cell fate decisions during proepicardial/septum transversum (PE/ST) development in chicken, with distinct regulation by Bmp2 and Fgf2.
Purpose of the Study:
- To investigate the functional roles of Bmp and Fgf signaling in mouse PE/ST development.
- To determine the impact of these signaling pathways on microRNA regulation and cardiac lineage determination in mice.
- To compare mouse PE/ST development with previously observed chicken models.
Main Methods:
- Mouse PE/ST explants and epicardial/endocardial cell cultures were treated with Bmp and Fgf family members.
- Quantitative Polymerase Chain Reaction (qPCR) was used to analyze miRNA expression, cardiomyogenic and fibrogenic differentiation markers, and epithelial-to-mesenchymal transition (EMT) markers.
- RNA sequencing (RNAseq) was performed on mouse PE/ST and embryonic epicardium.
Main Results:
- Bmp2/Bmp4 and Fgf2/Fgf8 signaling did not induce cardiomyogenesis, fibrogenesis, or EMT in mouse PE/ST explants.
- Despite the lack of induction, deregulation of several microRNAs was observed in mouse PE/ST explants.
- RNAseq identified novel Bmp and Fgf family members in mouse PE/ST and embryonic epicardium, but their role in EMT and differentiation was limited.
Conclusions:
- Mouse PE/ST development exhibits distinct responses to Bmp and Fgf signaling compared to chicken PE/ST.
- The findings suggest limited involvement of tested Bmp and Fgf signaling in inducing EMT and cardiomyogenic/fibrogenic differentiation in mouse PE/ST.
- Species-specific differences are critical in regulating PE/ST cardiomyogenic lineage commitment.
