Mending broken hearts: cardiac development as a basis for adult heart regeneration and repair
Open accessAbstract
As the adult mammalian heart has limited potential for regeneration and repair, the loss of cardiomyocytes during injury and disease can result in heart failure and death. The cellular processes and regulatory mechanisms involved in heart growth and development can be exploited to repair the injured adult heart through 'reawakening' pathways that are active during embryogenesis. Heart function has been restored in rodents by reprogramming non-myocytes into cardiomyocytes, by expressing transcription factors (GATA4, HAND2, myocyte-specific enhancer factor 2C (MEF2C) and T-box 5 (TBX5)) and microRNAs (miR-1, miR-133, miR-208 and miR-499) that control cardiomyocyte identity. Stimulating cardiomyocyte dedifferentiation and proliferation by activating mitotic signalling pathways involved in embryonic heart growth represents a complementary approach for heart regeneration and repair. Recent advances in understanding the mechanistic basis of heart development offer exciting opportunities for effective therapies for heart failure.
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Yap loss- or gain-of-function in the embryonic heart is frequently lethal.
“Several studies show that Yap loss- or gainof-function in the embryonic heart is frequently lethal (reviewed by (84, 141, 155)).”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [155]
The section “Inactivation of Hippo signalling promotes proliferation” reports that Yap deletion in the embryonic heart caused embryonic lethality. It says YAP gain of function stimulates cardiomyocyte proliferation, but does not say it is lethal. The review also does not establish that lethality occurs frequently. (LLM, conf=0.88)
Experimental — accuracy not yet measured
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A Common Progenitor at the Heart of Development
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YAP/TAZ upstream signals and downstream responses
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- Authors
- Xin, M., Olson, E. N., & Bassel-Duby, R.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Olson, Eric N.
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2013-07-10
- Volume
- 14
- Issue
- 8
- Pages
- 529-541
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC3757945
- OpenAlex
- W2015644748
- Cited by
- 514
- References
- 114
- Citations by year
- 2026: 17 · 2025: 24 · 2024: 37 · 2023: 34 · 2022: 34 · 2021: 34 · 2020: 42 · 2019: 47 · 2018: 51 · 2017: 47 · 2016: 47 · 2015: 55 · 2014: 38 · 2013: 5 · 2012: 1
- FWCI
- 4.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Welch Foundation
- Aurora Foundation
- National Institutes of Health (5u01hl100401-07)
- National Heart, Lung, and Blood Institute (R01HL111665, R01HL077439, U01-HL-100401, R01HL093039)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK099653)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- cardiac regeneration, heart development, heart failure, cardiomyocyte dedifferentiation, cardiomyocyte proliferation, transcription factors, microRNA, cardiac repair
- MeSH terms
- Adult, Animals, Heart, Humans, Models, Biological, Regeneration, Wound Healing, Myocytes, Cardiac, Regenerative Medicine, Embryonic Development
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