Myocardial Notch1-Rbpj deletion does not affect NOTCH signaling, heart development or function.
During vertebrate cardiac development NOTCH signaling activity in the endocardium is essential for the crosstalk between endocardium and myocardium that initiates ventricular trabeculation and valve primordium formation. This crosstalk leads later to the maturation and compaction of the ventricular...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0203100 |
| _version_ | 1823961926759088128 |
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| author | Alejandro Salguero-Jiménez Joaquim Grego-Bessa Gaetano D'Amato Luis J Jiménez-Borreguero José Luis de la Pompa |
| author_facet | Alejandro Salguero-Jiménez Joaquim Grego-Bessa Gaetano D'Amato Luis J Jiménez-Borreguero José Luis de la Pompa |
| author_sort | Alejandro Salguero-Jiménez |
| collection | DOAJ |
| description | During vertebrate cardiac development NOTCH signaling activity in the endocardium is essential for the crosstalk between endocardium and myocardium that initiates ventricular trabeculation and valve primordium formation. This crosstalk leads later to the maturation and compaction of the ventricular chambers and the morphogenesis of the cardiac valves, and its alteration may lead to disease. Although endocardial NOTCH signaling has been shown to be crucial for heart development, its physiological role in the myocardium has not been clearly established. Here we have used mouse genetics to evaluate the role of NOTCH in myocardial development. We have inactivated the unique and ubiquitous NOTCH effector RBPJ in early cardiomyocytes progenitors, and examined its consequences in cardiac development and function. Our results show that mice with Tnnt2-Cre-mediated myocardial-specific deletion of Rbpj develop to term, with homozygous mutant animals showing normal expression of cardiac development markers, and normal adult heart function. Similar observations have been obtained after Notch1 deletion with Tnnt2-Cre. We have also deleted Rbpj in both myocardial and endocardial progenitor cells, using the Nkx2.5-Cre driver, resulting in ventricular septal defect (VSD), double outlet right ventricle (DORV), and bicuspid aortic valve (BAV), due to NOTCH signaling abrogation in the endocardium of cardiac valves. Our data demonstrate that NOTCH-RBPJ inactivation in the myocardium does not affect heart development or adult cardiac function. |
| first_indexed | 2024-12-17T17:11:16Z |
| format | Article |
| id | doaj.art-ec82dc3876b8451197920a6a45b2c0ed |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T17:11:16Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ec82dc3876b8451197920a6a45b2c0ed2022-12-21T21:40:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011312e020310010.1371/journal.pone.0203100Myocardial Notch1-Rbpj deletion does not affect NOTCH signaling, heart development or function.Alejandro Salguero-JiménezJoaquim Grego-BessaGaetano D'AmatoLuis J Jiménez-BorregueroJosé Luis de la PompaDuring vertebrate cardiac development NOTCH signaling activity in the endocardium is essential for the crosstalk between endocardium and myocardium that initiates ventricular trabeculation and valve primordium formation. This crosstalk leads later to the maturation and compaction of the ventricular chambers and the morphogenesis of the cardiac valves, and its alteration may lead to disease. Although endocardial NOTCH signaling has been shown to be crucial for heart development, its physiological role in the myocardium has not been clearly established. Here we have used mouse genetics to evaluate the role of NOTCH in myocardial development. We have inactivated the unique and ubiquitous NOTCH effector RBPJ in early cardiomyocytes progenitors, and examined its consequences in cardiac development and function. Our results show that mice with Tnnt2-Cre-mediated myocardial-specific deletion of Rbpj develop to term, with homozygous mutant animals showing normal expression of cardiac development markers, and normal adult heart function. Similar observations have been obtained after Notch1 deletion with Tnnt2-Cre. We have also deleted Rbpj in both myocardial and endocardial progenitor cells, using the Nkx2.5-Cre driver, resulting in ventricular septal defect (VSD), double outlet right ventricle (DORV), and bicuspid aortic valve (BAV), due to NOTCH signaling abrogation in the endocardium of cardiac valves. Our data demonstrate that NOTCH-RBPJ inactivation in the myocardium does not affect heart development or adult cardiac function.https://doi.org/10.1371/journal.pone.0203100 |
| spellingShingle | Alejandro Salguero-Jiménez Joaquim Grego-Bessa Gaetano D'Amato Luis J Jiménez-Borreguero José Luis de la Pompa Myocardial Notch1-Rbpj deletion does not affect NOTCH signaling, heart development or function. PLoS ONE |
| title | Myocardial Notch1-Rbpj deletion does not affect NOTCH signaling, heart development or function. |
| title_full | Myocardial Notch1-Rbpj deletion does not affect NOTCH signaling, heart development or function. |
| title_fullStr | Myocardial Notch1-Rbpj deletion does not affect NOTCH signaling, heart development or function. |
| title_full_unstemmed | Myocardial Notch1-Rbpj deletion does not affect NOTCH signaling, heart development or function. |
| title_short | Myocardial Notch1-Rbpj deletion does not affect NOTCH signaling, heart development or function. |
| title_sort | myocardial notch1 rbpj deletion does not affect notch signaling heart development or function |
| url | https://doi.org/10.1371/journal.pone.0203100 |
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