Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function.
The homeodomain transcription factor NKX2-5 is known to be essential for both normal heart development and for heart function. But little is yet known about the identities of its downstream effectors or their function during differentiation of cardiac progenitor cells (CPCs). We have used transgenic...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0212992 |
| _version_ | 1819292585108176896 |
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| author | Laurent Dupays Norma Towers Sophie Wood Anna David Daniel J Stuckey Timothy Mohun |
| author_facet | Laurent Dupays Norma Towers Sophie Wood Anna David Daniel J Stuckey Timothy Mohun |
| author_sort | Laurent Dupays |
| collection | DOAJ |
| description | The homeodomain transcription factor NKX2-5 is known to be essential for both normal heart development and for heart function. But little is yet known about the identities of its downstream effectors or their function during differentiation of cardiac progenitor cells (CPCs). We have used transgenic analysis and CRISPR-mediated ablation to identify a cardiac enhancer of the Furin gene. The Furin gene, encoding a proprotein convertase, is directly repressed by NKX2-5. Deletion of Furin in CPCs is embryonic lethal, with mutant hearts showing a range of abnormalities in the outflow tract. Those defects are associated with a reduction in proliferation and premature differentiation of the CPCs. Deletion of Furin in differentiated cardiomyocytes results in viable adult mutant mice showing an elongation of the PR interval, a phenotype that is consistent with the phenotype of mice and human mutant for Nkx2-5. Our results show that Furin mediate some aspects of Nkx2-5 function in the heart. |
| first_indexed | 2024-12-24T03:56:52Z |
| format | Article |
| id | doaj.art-4ef8b6bea167496baa3ccfbb3d271c80 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-24T03:56:52Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4ef8b6bea167496baa3ccfbb3d271c802022-12-21T17:16:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01143e021299210.1371/journal.pone.0212992Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function.Laurent DupaysNorma TowersSophie WoodAnna DavidDaniel J StuckeyTimothy MohunThe homeodomain transcription factor NKX2-5 is known to be essential for both normal heart development and for heart function. But little is yet known about the identities of its downstream effectors or their function during differentiation of cardiac progenitor cells (CPCs). We have used transgenic analysis and CRISPR-mediated ablation to identify a cardiac enhancer of the Furin gene. The Furin gene, encoding a proprotein convertase, is directly repressed by NKX2-5. Deletion of Furin in CPCs is embryonic lethal, with mutant hearts showing a range of abnormalities in the outflow tract. Those defects are associated with a reduction in proliferation and premature differentiation of the CPCs. Deletion of Furin in differentiated cardiomyocytes results in viable adult mutant mice showing an elongation of the PR interval, a phenotype that is consistent with the phenotype of mice and human mutant for Nkx2-5. Our results show that Furin mediate some aspects of Nkx2-5 function in the heart.https://doi.org/10.1371/journal.pone.0212992 |
| spellingShingle | Laurent Dupays Norma Towers Sophie Wood Anna David Daniel J Stuckey Timothy Mohun Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function. PLoS ONE |
| title | Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function. |
| title_full | Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function. |
| title_fullStr | Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function. |
| title_full_unstemmed | Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function. |
| title_short | Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function. |
| title_sort | furin a transcriptional target of nkx2 5 has an essential role in heart development and function |
| url | https://doi.org/10.1371/journal.pone.0212992 |
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