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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/316417bd8282469f99bf1ef61ce4476a
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spelling	oai:doaj.org-article:316417bd8282469f99bf1ef61ce4476a2021-12-02T20:03:17ZHistone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish.1553-73901553-740410.1371/journal.pgen.1009890https://doaj.org/article/316417bd8282469f99bf1ef61ce4476a2021-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009890https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404In 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.Anja BühlerBernd M GahrDeung-Dae ParkAlberto BertozziAlena BoosMohankrishna DalvoyAlexander PottFranz OswaldRhett A KovallBernhard KühnGilbert WeidingerWolfgang RottbauerSteffen JustPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 11, p e1009890 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 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.
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.
format	article
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
title	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_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_sort	histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/316417bd8282469f99bf1ef61ce4476a
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Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish.

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