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dc.contributor.authorSalguero-Jimenez, Alejandro 
dc.contributor.authorGrego-Bessa, Joaquim 
dc.contributor.authorD'Amato, Gaetano 
dc.contributor.authorJimenez-Borreguero, Luis J 
dc.contributor.authorde la Pompa, Jose Luis 
dc.date.accessioned2019-02-06T08:09:42Z
dc.date.available2019-02-06T08:09:42Z
dc.date.issued2018
dc.identifier.citationPLoS One. 2018; 13(12):e0203100es_ES
dc.identifier.issn1932-6203es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7125
dc.description.abstractDuring 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.es_ES
dc.description.sponsorshipThis study was funded by grants SAF2016-78370-R, CB16/11/00399 (CIBER CV) and RD16/0011/0021 (TERCEL) from the the Spanish Ministry of Science, Innovation and Universities (MCIU) and grants from the Fundacion BBVA (Ref.: BIO14_298) and Fundacion La Marato (Ref.: 20153431) to JLDLP. AS-J holds a FPU fellowship from the Ministerio de Educacion, Cultura y Deporte of Spain. JG-B is funded by the Programa de Atraccion de Talento of the Comunidad de Madrid (2016T1/BMD1540). The cost of this publication was supported in part with FEDER funds. The CNIC (https://www.cnic.es/en) is supported by the MEIC and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).es_ES
dc.language.isoenges_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleMyocardial Notch1-Rbpj deletion does not affect NOTCH signaling, heart development or functiones_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID30596653es_ES
dc.format.volume13es_ES
dc.format.number12es_ES
dc.format.pagee0203100es_ES
dc.identifier.doi10.1371/journal.pone.0203100es_ES
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España) 
dc.contributor.funderFundación BBVA 
dc.contributor.funderFundación La Marató TV3 
dc.contributor.funderMinisterio de Educación, Cultura y Deporte (España) 
dc.contributor.funderComunidad de Madrid (España) 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderFundación ProCNIC 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1932-6203es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pone.0203100es_ES
dc.identifier.journalPloS onees_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Señalización Intercelular durante el Desarrollo y la Enfermedad Cardiovasculares_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2016-78370-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CB16/11/00399es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.rights.accessRightsopen accesses_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/MINECO//RD16%2F0011%2F0021/ES/Red de Terapia Celular (TerCel)/ 


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Atribución 4.0 Internacional
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