PUBLICATION

Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish

Authors
Bühler, A., Gahr, B.M., Park, D.D., Bertozzi, A., Boos, A., Dalvoy, M., Pott, A., Oswald, F., Kovall, R.A., Kühn, B., Weidinger, G., Rottbauer, W., Just, S.
ID
ZDB-PUB-211103-2
Date
2021
Source
PLoS Genetics   17: e1009890 (Journal)
Registered Authors
Boos, Alena, Bühler, Anja, Dalvoy, Mohankrishna, Gahr, Bernd, Just, Steffen, Park, Deung-Dae, Pott, Alexander, Rottbauer, Wolfgang, Weidinger, Gilbert
Keywords
none
MeSH Terms
  • Heart/physiology*
  • Animals
  • Zebrafish Proteins/metabolism*
  • Cell Proliferation
  • Histone Deacetylase 1/metabolism*
  • Zebrafish/embryology*
  • Regeneration/physiology*
  • Myocytes, Cardiac/cytology*
(all 8)
PubMed
34723970 Full text @ PLoS Genet.
Abstract
In contrast to mammals, the zebrafish maintains its cardiomyocyte proliferation capacity throughout adulthood. However, neither the molecular mechanisms that orchestrate the proliferation of cardiomyocytes during developmental heart growth nor in the context of regeneration in the adult are sufficiently defined yet. We identified in a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen the recessive, embryonic-lethal zebrafish mutant baldrian (bal), which shows severely impaired developmental heart growth due to diminished cardiomyocyte proliferation. By positional cloning, we identified a missense mutation in the zebrafish histone deacetylase 1 (hdac1) gene leading to severe protein instability and the loss of Hdac1 function in vivo. Hdac1 inhibition significantly reduces cardiomyocyte proliferation, indicating a role of Hdac1 during developmental heart growth in zebrafish. To evaluate whether developmental and regenerative Hdac1-associated mechanisms of cardiomyocyte proliferation are conserved, we analyzed regenerative cardiomyocyte proliferation after Hdac1 inhibition at the wound border zone in cryoinjured adult zebrafish hearts and we found that Hdac1 is also essential to orchestrate regenerative cardiomyocyte proliferation in the adult vertebrate heart. In summary, our findings suggest an important and conserved role of Histone deacetylase 1 (Hdac1) in developmental and adult regenerative cardiomyocyte proliferation in the vertebrate heart.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
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Citation
Bühler, A., Gahr, B.M., Park, D.D., Bertozzi, A., Boos, A., Dalvoy, M., Pott, A., Oswald, F., Kovall, R.A., Kühn, B., Weidinger, G., Rottbauer, W., Just, S. (2021) Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish. PLoS Genetics. 17:e1009890.