Regulatory modulation of the T-box gene Tbx5 links development, evolution, and adaptation of the sternum
Open accessAbstract
Significance: The fin-to-limb transition and acquisition of sterna were critical steps in the evolution of tetrapods, but despite the importance of the sternum in enabling quadrupedal locomotion and avian flight, the mechanisms controlling acquisition and evolutionary adaptation of sterna are not understood. Furthermore, the mechanisms that underlie sternum development and sternal defects are not known. We describe T-box transcription factor gene Tbx5 function in sternum formation, how disruption of TBX5 causes human sternum defects, and how modulation of Tbx5 was key to acquisition and adaptation of sterna in vertebrates. We also demonstrate a quantitative correlation between sternum dimensions and forelimb use in avian species.
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Both TBX3 and TBX5 are involved in bone development and remodeling.
“Among other functions, both proteins are involved in bone development [18–20] and remodeling [21].”
From The oncoprotein TBX3 is controlling severity in experimental arthritis (2019) · cites this paper as [20]
The paper’s section on the early requirement for Tbx5 in sternum development reports that mice lacking Tbx5 fail to form a sternum, supporting a role for TBX5 in skeletal development. It does not establish a role for TBX3. In the citing sentence, remodeling has a separate citation [21], so it is not attributed to this source. (LLM, conf=0.85)
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- Authors
- Bickley, S. R. B., & Logan, M. P. O.
- Affiliations
- National Institute for Medical Research (GB)
- King's College London (GB)
- ORCID
- Logan, Malcolm P. O.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-12-02
- Volume
- 111
- Issue
- 50
- Pages
- 17917-17922
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4273354
- OpenAlex
- W1965428988
- Cited by
- 46
- References
- 34
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 8 · 2019: 7 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 3
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- Funders
- Children’s Hospital of Wisconsin Research Institute
- Murdoch Children's Research Institute
- University of Cambridge
- Medical Research Council (MC_PC_13052)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Developmental Biology › Congenital limb and hand anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- TBX5, forelimb development, Holt-Oram syndrome, lateral plate mesoderm, emu, flightless birds, skeletal evolution, T-box transcription factor
- MeSH terms
- Adaptation, Biological, Animals, Body Weights and Measures, Chick Embryo, Biological Evolution, Fluorescent Antibody Technique, Forelimb, Morphogenesis, Species Specificity, Sternum, In Situ Hybridization, T-Box Domain Proteins, Mice
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