2026-04-29T04:09:26Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/71252024-09-27T09:54:55Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Salguero-Jimenez, Alejandro
author
Grego-Bessa, Joaquim
author
D'Amato, Gaetano
author
Jimenez-Borreguero, Luis J
author
de la Pompa, Jose Luis
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Fundación BBVA
funder
Fundación La Marató TV3
funder
Ministerio de Educación, Cultura y Deporte (España)
funder
Comunidad de Madrid (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación ProCNIC
2019-02-06T08:09:42Z
2019-02-06T08:09:42Z
2018
PLoS One. 2018; 13(12):e0203100
1932-6203
http://hdl.handle.net/20.500.12105/7125
30596653
10.1371/journal.pone.0203100
1932-6203
PloS one
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.
eng
Myocardial Notch1-Rbpj deletion does not affect NOTCH signaling, heart development or function
journal article
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MyocardialNotch1-RbpjDeletionDoes_2018.pdf
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MyocardialNotch1-RbpjDeletionDoes_2018.pdf.txt