Cited by 10Congenital heart defects researchDevelopmental Biology and Gene RegulationMicroRNA in disease regulation

The role of bmp- and fgf signaling modulating mouse proepicardium cell fate

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Garcia-Padilla, Carlos, Hernandez-Torres, Francisco, Lozano-Velasco, Estefania, Dueñas, Angel, Muñoz-Gallardo, Maria del Mar, Garcia-Valencia, Isabel S., Palencia-Vincent, Lledó, Aranega, Amelia +1 more·2022·Frontiers in Cell and Developmental Biology

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.

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Crossref · 10.3389/fcell.2021.757781

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  • miR-23 is involved in regulating cardiac development in several species such as zebrafish, mice, and chickens.

    “miR-23 is involved in regulating the cardiac development in several species such as zebrafish, mice, and chickens.”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [121]

    The Abstract says miR-23 overexpression blocked proepicardium-derived cardiomyogenesis in chicken, and the Results discuss miR-23b in mouse proepicardial explants. The Discussion also links miR-23 to endocardial cushion formation. Our copy does not report a role for miR-23 in zebrafish cardiac development, so the three-species claim is not fully supported. Page numbers were not available in the indexed passages. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • In zebrafish and mice, miR-23 within the embryonic heart is essential to confine endocardial cushion formation by inhibiting Has2 and extracellular hyaluronic acid production.

    “In zebrafish and mice, miR-23 within the embryonic heart is essential to confine endocardial cushion formation by inhibiting the expression of hyaluronic acid synthase 2 (Has2) and extracellular hyaluronic acid production.”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [121]

    The Discussion (page unavailable) reports a role for miR-23 in endocardial cushion formation. It does not say that miR-23 confines cushion formation in zebrafish and mice, or that it inhibits Has2 expression and extracellular hyaluronic acid production. Searches for Has2 and hyaluronic acid found no supporting passage in our copy. (LLM, conf=0.86)

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  • In chickens and mice, over-expression of miR-23 during the early stages of myocardial formation hinders the generation of myocardium in the epicardial/transverse membrane.

    “Further evidence from chickens and mice has indicated that the over-expression of miR-23 during the early stages of myocardial formation hinders the generation of myocardium in the epicardial/transverse membrane [120,121].”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [121]

    The Results section (‘Bmp and Fgf Signalling in Mouse PE E9.5 Explants’; page unavailable) groups miR-23b among microRNAs that ‘do not enhance or even inhibit’ PE/ST-derived cardiomyogenesis. It does not establish that miR-23 overexpression hinders myocardial formation in both chickens and mice: the mouse experiments described there measure miR-23b expression after growth-factor treatment, not the effect of miR-23 overexpression. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Authors
Garcia-Padilla, C., Hernandez-Torres, F., Lozano-Velasco, E., Dueñas, A., Muñoz-Gallardo, M. D. M., Garcia-Valencia, I. S., Palencia-Vincent, L., Aranega, A., & Franco, D.
Affiliations
Universidad de Jaén (ES)
Corresponding author
Franco, Diego
Venue
Frontiers in Cell and Developmental Biology
Published
2022-01-04
Volume
9
Pages
757781-757781
ISSN
2296-634X (ISSN-L)
OpenAlex
W4205293350
Cited by
10
References
89
Citations by year
2026: 2 · 2025: 4 · 2024: 3 · 2023: 1
FWCI
0.65
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RUJA (Universidad de Jaén) (acceptedVersion, cc-by-nc-nd)
  • Institutional Repository of the University of Granada (University of Granada) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ministerio de Ciencia, Innovación y Universidades
  • Consejería de Conocimiento, Investigación y Universidad, Junta de Andalucía
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
proepicardium, septum transversum, BMP signaling, FGF signaling, microRNA, cardiomyogenesis, epithelial-mesenchymal transition, fibrogenesis, cell fate determination, species differences, mouse embryo

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