Myocardial Bmp2 gain causes ectopic EMT and promotes cardiomyocyte proliferation and immaturity
Open accessAbstract
During mammalian heart development, restricted myocardial Bmp2 expression is a key patterning signal for atrioventricular canal specification and the epithelial–mesenchyme transition that gives rise to the valves. Using a mouse transgenic line conditionally expressing Bmp2 , we show that widespread Bmp2 expression in the myocardium leads to valve and chamber dysmorphogenesis and embryonic death by E15.5. Transgenic embryos show thickened valves, ventricular septal defect, enlarged trabeculae and dilated ventricles, with an endocardium able to undergo EMT both in vivo and in vitro. Gene profiling and marker analysis indicate that cellular proliferation is increased in transgenic embryos, whereas chamber maturation and patterning are impaired. Similarly, forced Bmp2 expression stimulates proliferation and blocks cardiomyocyte differentiation of embryoid bodies. These data show that widespread myocardial Bmp2 expression directs ectopic valve primordium formation and maintains ventricular myocardium and cardiac progenitors in a primitive, proliferative state, identifying the potential of Bmp2 in the expansion of immature cardiomyocytes.
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In the Bmp2fl/fl;Nkx2-5-cre phenotype, AV cushions and mesenchyme are absent due to failure to initiate EndMT.
“This is in line with the Bmp2fl/fl;Nkx2-5-cre phenotype, where AV cushions and mesenchyme are absent due to the failure to initiate EndMT10,58.”
From Cell diversity and plasticity during atrioventricular heart valve EMTs (2023) · cites this paper as [58]
The Results section on rescue of AVC specification reports an AVC specification defect in Nkx2.5Cre;Bmp2flox/flox mutants and shows that restoring Bmp2 rescues it (page unavailable). It does not state that AV cushions and mesenchyme are absent in those mutants or establish failure to initiate EndMT as the cause. The reported abundant cushion mesenchyme belongs to a different, Bmp2-overexpressing genotype. (LLM, conf=0.83)
Experimental — accuracy not yet measuredMyocardial cues are predicted as the main drivers of EndMT.
“Of note, myocardial cues are predicted as the main drivers of EndMT (Supplementary Fig. 7b), which agrees with previous analyses that assessed AV identity induction7,58.”
From Cell diversity and plasticity during atrioventricular heart valve EMTs (2023) · cites this paper as [58]
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- Authors
- Prados, B., Gómez-Apiñániz, P., Papoutsi, T., Luxán, G., Zaffran, S., Pérez-Pomares, J. M., & de la Pompa, J. L.
- Affiliations
- Spanish National Centre for Cardiovascular Research (ES)
- Inserm (FR)
- Andalusian Centre for Nanomedicine and Biotechnology (ES)
- Venue
- Cell Death & Disease
- Published
- 2018-03-14
- Volume
- 9
- Issue
- 3
- Pages
- 399-399
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC5852166
- OpenAlex
- W2791856025
- Cited by
- 35
- References
- 49
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 7 · 2020: 2 · 2019: 2 · 2018: 1
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Death and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by)
- HAL (submittedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Fundación BBVA (BIO14_298)
- Banco Bilbao Vizcaya Argentaria
- Centro Nacional de Investigaciones Cardiovasculares (SEV‐2015‐0505)
- Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España (RD16/0011/0021, SAF2016-78370-R, CB16/11/00399, SEV-2015-0505)
- 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 › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- BMP-2, myocardium, epithelial-mesenchymal transition, valve development, atrioventricular canal, ventricular septal defect, cardiomyocyte proliferation, cardiomyocyte differentiation, cardiac progenitor cells, heart development, embryonic lethality, embryoid bodies
- MeSH terms
- Animals, Heart, Mice, Transgenic, Myocardium, Signal Transduction, Gene Expression Regulation, Developmental, Myocytes, Cardiac, Cell Proliferation, Mice, Bone Morphogenetic Protein 2, Epithelial-Mesenchymal Transition
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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