Temporal and Distinct TGFβ Ligand Requirements during Mouse and Avian Endocardial Cushion Morphogenesis
Open accessAbstract
The formation of endocardial cushions in the atrioventricular (AV) canal of the rudimentary heart requires epithelial-to-mesenchymal cell transformation (EMT). This is a complex developmental process regulated by multiple extracellular signals and transduction pathways. A collagen gel assay, long used to examine endocardial cushion development in avian models, is now being employed to investigate genetically engineered mouse models with abnormal heart morphogenesis. In this study, we determine interspecies variations for avian and mouse cultured endocardial cushion explants. Considering these observed morphologic differences, we also define the temporal requirements for TGFbeta2 and TGFbeta3 during mouse endocardial cushion morphogenesis. TGFbeta2 and TGFbeta3 blocking antibodies inhibit endothelial cell activation and transformation, respectively, in avian explants. In contrast, neutralizing TGFbeta2 inhibits cell transformation in the mouse, while TGFbeta3 antibodies have no effect on activation or transformation events. This functional requirement for TGFbeta2 is concomitant with expression of TGFbeta2, but not TGFbeta3, within mouse endocardial cushions at a time coincident with transformation. Thus, both TGFbeta2 and TGFbeta3 appear necessary for the full morphogenetic program of EMT in the chick, but only TGFbeta2 is expressed and obligatory for mammalian endocardial cushion cell 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 [67]
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References 36 · Cited by 279
Research works printed but not linked: 2
- Kaufman, M. H., and Bard, J. B. L. (1999). "The Anatomical Basis of Mouse Development." Academic Press, San Diego.
- Potts, J. D., Dagle, J. M., Walder, J. A., Weeks, D. L., and Runyan, R. B. (1991). Epithelial-mesenchymal transformation of embry- onic cardiac endothelial cells is inhibited by a modified antisense oligodeoxynucleotide to transforming growth factor beta 3. Proc. Natl. Acad. Sci. USA 88, 1516 -1520.
- Authors
- Camenisch, T. D., Molin, D. G. M., Person, A., Runyan, R. B., Gittenberger-de Groot, A. C., McDonald, J. A., & Klewer, S. E.
- Affiliations
- Mayo Clinic (US)
- Leiden University Medical Center (NL)
- University of Arizona (US)
- University of Utah (US)
- Corresponding author
- Camenisch, Todd D.
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 248
- Issue
- 1
- Pages
- 170-181
- ISSN
- 0012-1606 (ISSN-L)
- OpenAlex
- W2000865482
- Cited by
- 279
- References
- 36
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 10 · 2023: 6 · 2022: 1 · 2021: 11 · 2020: 10 · 2019: 7 · 2018: 10 · 2017: 8 · 2016: 9 · 2015: 16 · 2014: 14 · 2013: 11 · 2012: 18
- FWCI
- 6.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 4003 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- W. M. Keck Foundation
- American Heart Association
- Mayo Foundation for Medical Education and Research
- National Institutes of Health (1f32hl010299-01, 5p50hl042266-09)
- National Heart, Lung, and Blood Institute (P01HL063926, P50-HL-42266, F32 HL 10299, P01 HL 63926)
- 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 › TGF-β signaling in diseases
- Keywords
- TGF-beta2, TGF-beta3, epithelial-mesenchymal transition, atrioventricular canal, heart development, chick embryo, mouse embryo, species differences, endothelial activation
- MeSH terms
- Actins, Animals, Birds, Cell Differentiation, Chick Embryo, Collagen, Endocardium, Heart Septum, Immunohistochemistry, Ligands, Models, Biological, Time Factors, Transforming Growth Factor beta, In Situ Hybridization, Mice, Transforming Growth Factor beta2, Transforming Growth Factor beta3
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