Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish.
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 sufficie...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-11-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1009890 |
| _version_ | 1818361055846334464 |
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| author | Anja Bühler Bernd M Gahr Deung-Dae Park Alberto Bertozzi Alena Boos Mohankrishna Dalvoy Alexander Pott Franz Oswald Rhett A Kovall Bernhard Kühn Gilbert Weidinger Wolfgang Rottbauer Steffen Just |
| author_facet | Anja Bühler Bernd M Gahr Deung-Dae Park Alberto Bertozzi Alena Boos Mohankrishna Dalvoy Alexander Pott Franz Oswald Rhett A Kovall Bernhard Kühn Gilbert Weidinger Wolfgang Rottbauer Steffen Just |
| author_sort | Anja Bühler |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T21:10:36Z |
| format | Article |
| id | doaj.art-316417bd8282469f99bf1ef61ce4476a |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-13T21:10:36Z |
| publishDate | 2021-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-316417bd8282469f99bf1ef61ce4476a2022-12-21T23:31:21ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-11-011711e100989010.1371/journal.pgen.1009890Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish.Anja BühlerBernd M GahrDeung-Dae ParkAlberto BertozziAlena BoosMohankrishna DalvoyAlexander PottFranz OswaldRhett A KovallBernhard KühnGilbert WeidingerWolfgang RottbauerSteffen JustIn 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.https://doi.org/10.1371/journal.pgen.1009890 |
| spellingShingle | Anja Bühler Bernd M Gahr Deung-Dae Park Alberto Bertozzi Alena Boos Mohankrishna Dalvoy Alexander Pott Franz Oswald Rhett A Kovall Bernhard Kühn Gilbert Weidinger Wolfgang Rottbauer Steffen Just Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish. PLoS Genetics |
| title | Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish. |
| title_full | Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish. |
| title_fullStr | Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish. |
| title_full_unstemmed | Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish. |
| title_short | Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish. |
| title_sort | histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish |
| url | https://doi.org/10.1371/journal.pgen.1009890 |
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