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Cited by 376Congenital heart defects researchDevelopmental Biology and Gene RegulationWnt/β-catenin signaling in development and cancer

β-Catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse

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Liebner, Stefan, Cattelino, Anna, Gallini, Radiosa, Rudini, Noemi, Iurlaro, Monica, Piccolo, Stefano, Dejana, Elisabetta·2004·The Journal of Cell Biology
DOI 10.1083/jcb.200403050PMC PMC2172268
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Abstract

During heart development endocardial cells within the atrio-ventricular (AV) region undergo TGFβ-dependent epithelial-mesenchymal transformation (EMT) and invade the underlying cardiac jelly. This process gives rise to the endocardial cushions from which AV valves and part of the septum originate. In this paper we show that in mouse embryos and in AV explants TGFβ induction of endocardial EMT is strongly inhibited in mice deficient for endothelial β-catenin, leading to a lack of heart cushion formation. Using a Wnt-signaling reporter mouse strain, we demonstrated in vivo and ex vivo that EMT in heart cushion is accompanied by activation of β-catenin/TCF/Lef transcriptional activity. In cultured endothelial cells, TGFβ2 induces α-smooth muscle actin (αSMA) expression. This process was strongly reduced in β-catenin null cells, although TGFβ2 induced smad phosphorylation was unchanged. These data demonstrate an involvement of β-catenin/TCF/Lef transcriptional activity in heart cushion formation, and suggest an interaction between TGFβ and Wnt-signaling pathways in the induction of endothelial-mesenchymal transformation.

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  • NicheNet analysis identifies activation of signalling pathways classically associated with EndMT initiation and mesenchymal development, including TGFβ superfamily, WNT, VEGF, and FGF signalling, signalling toward endocardial cells at E10.5.

    “In our analysis, we see the activation of signalling pathways classically associated with EndMT initiation and mesenchymal development, including TGFβ superfamily9,10,67, WNT18, VEGF68,69, and FGF70 signalling.”

    From Cell diversity and plasticity during atrioventricular heart valve EMTs (2023) · cites this paper as [18]

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Cited by

Sorted by citations

Authors
Liebner, S., Cattelino, A., Gallini, R., Rudini, N., Iurlaro, M., Piccolo, S., & Dejana, E.
Affiliations
  • University of Milan (IT)
  • University of Padua (IT)
Corresponding author
Dejana, Elisabetta
ORCID
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2004-08-02
Volume
166
Issue
3
Pages
359-367
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.200403050
PMC
PMC2172268
OpenAlex
W2149223832
Cited by
376
References
1
Citations by year
2026: 7 · 2025: 6 · 2024: 5 · 2023: 11 · 2022: 11 · 2021: 16 · 2020: 17 · 2019: 12 · 2018: 23 · 2017: 24 · 2016: 20 · 2015: 13 · 2014: 17 · 2013: 27 · 2012: 24
FWCI
6.86
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • Padua Research Archive (University of Padova) (submittedVersion, other-oa)
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 › Wnt/β-catenin signaling in development and cancer
Keywords
β-catenin, endocardial cushion, TGF-beta signaling, Wnt signaling, TCF/LEF transcription, alpha-smooth muscle actin, atrioventricular valves, cardiac jelly, Smad phosphorylation, mouse embryo
MeSH terms
Snail Family Transcription Factors, Cadherin 5, Animals, Cell Differentiation, Cytoskeletal Proteins, DNA-Binding Proteins, Endothelium, Heart Septum, Membrane Proteins, Mesoderm, Receptors, Cell Surface, Transcription Factors, Trans-Activators, Antigens, CD, Cadherins, Transforming Growth Factor beta, Intracellular Signaling Peptides and Proteins, beta Catenin, Mice, Receptor, Notch1

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