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Reptilian heart development and the molecular basis of cardiac chamber evolution
Open accessAbstract
The emergence of terrestrial life witnessed the need for more sophisticated circulatory systems. This has evolved in birds, mammals and crocodilians into complete septation of the heart into left and right sides, allowing separate pulmonary and systemic circulatory systems, a key requirement for the evolution of endothermy. However, the evolution of the amniote heart is poorly understood. Reptilian hearts have been the subject of debate in the context of the evolution of cardiac septation: do they possess a single ventricular chamber or two incompletely septated ventricles? Here we examine heart development in the red-eared slider turtle, Trachemys scripta elegans (a chelonian), and the green anole, Anolis carolinensis (a squamate), focusing on gene expression in the developing ventricles. Both reptiles initially form a ventricular chamber that homogenously expresses the T-box transcription factor gene Tbx5. In contrast, in birds and mammals, Tbx5 is restricted to left ventricle precursors. In later stages, Tbx5 expression in the turtle (but not anole) heart is gradually restricted to a distinct left ventricle, forming a left-right gradient. This suggests that Tbx5 expression was refined during evolution to pattern the ventricles. In support of this hypothesis, we show that loss of Tbx5 in the mouse ventricle results in a single chamber lacking distinct identity, indicating a requirement for Tbx5 in septation. Importantly, misexpression of Tbx5 throughout the developing myocardium to mimic the reptilian expression pattern also results in a single mispatterned ventricular chamber lacking septation. Thus ventricular septation is established by a steep and correctly positioned Tbx5 gradient. Our findings provide a molecular mechanism for the evolution of the amniote ventricle, and support the concept that altered expression of developmental regulators is a key mechanism of vertebrate evolution.
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“Expression of this gene is confined to the left ventricle in the developing amniote heart but is expressed across the common ventricle in the three chambered reptile heart (Koshiba-Takeuchi et al., 2009).”
From Evolution of Gene Regulatory Networks Controlling Body Plan Development (2011) · cites this paper as Koshiba-Takeuchi et al., 2009
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“the tbx5 gene, deeply embedded in the vertebrate heart formation GRN (for review Davidson, 2006), turns out to be regulated differently during heart formation in reptiles than in birds and mammals, a Class-level difference.”
From Evolution of Gene Regulatory Networks Controlling Body Plan Development (2011) · cites this paper as Koshiba-Takeuchi et al., 2009
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“When uniform tbx5 expression was forced in the mouse heart, or left ventricle tbx5 expression was prevented, i.e., if a reptilian tbx5 spatial regulatory expression was imposed, the mouse developed a three-chambered heart lacking an interventricular septum.”
From Evolution of Gene Regulatory Networks Controlling Body Plan Development (2011) · cites this paper as Koshiba-Takeuchi et al., 2009
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Self-citationBMP10 is essential for maintaining cardiac growth during murine cardiogenesis
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Chamber-Specific Cardiac Expression of Tbx5 and Heart Defects in Holt–Oram Syndrome
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Goetze, J. P., Bruneau, B. G., Ramos, H. R., Ogawa, T., de Bold, M. L. K., & de Bold, A. J. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-020-0381-0 · Cited by 572
Self-citationEvolution of Gene Regulatory Networks Controlling Body Plan Development
Peter, I. S., & Davidson, E. H. (2011) · Cell · doi:10.1016/j.cell.2011.02.017 · Cited by 417
Signaling and Transcriptional Networks in Heart Development and RegenerationPreprint
Bruneau, B. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008292 · Cited by 295
Self-citationMyocardial Lineage Development
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Metadata
- Authors
- Koshiba-Takeuchi, K., Mori, A. D., Kaynak, B. L., Cebra-Thomas, J., Sukonnik, T., Georges, R. O., Latham, S., Beck, L., Henkelman, R. M., Black, B. L., Olson, E. N., Wade, J., Takeuchi, J. K., Nemer, M., Gilbert, S. F., & Bruneau, B. G.
- Affiliations
- Gladstone Institutes (US)
- Montreal Clinical Research Institute (CA)
- Michigan State University (US)
- University of Toronto (CA)
- University of California, San Francisco (US)
- The University of Texas Southwestern Medical Center (US)
- Tokyo Institute of Technology (JP)
- University of Ottawa (CA)
- Swarthmore College (US)
- Corresponding author
- Bruneau, Benoit G.
- ORCID
- Venue
- Nature
- Published
- 2009-09-03
- Volume
- 461
- Issue
- 7260
- Pages
- 95-98
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2753965
- OpenAlex
- W2025218263
- Cited by
- 182
- References
- 29
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 31 · 2023: 5 · 2022: 6 · 2021: 13 · 2020: 9 · 2019: 11 · 2018: 10 · 2017: 13 · 2016: 9 · 2015: 7 · 2014: 12 · 2013: 10 · 2012: 11
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Update notices
- erratum (2009-09-24)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Works - Scholarship, Research, & Creative Expression (Swarthmore College) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (1c06rr018928-01)
- National Heart, Lung, and Blood Institute (P01HL089707, R01HL064658)
- National Center for Research Resources (C06-RR-018928)
- 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
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- cardiac septation, TBX5, Anolis carolinensis, red-eared slider turtle, red-eared slider, left ventricle, endothermy evolution
- MeSH terms
- Animals, Chick Embryo, Heart, Lizards, Turtles, Gene Expression Regulation, Developmental, Evolution, Molecular, T-Box Domain Proteins, Organogenesis, Mice
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