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dc.contributor.author | Eley, Lorriane | |
dc.contributor.author | Alqahtani, Ahlam M. S. | |
dc.contributor.author | MacGrogan, Donal | |
dc.contributor.author | Richardson, Rachel V. | |
dc.contributor.author | Murphy, Lindsay | |
dc.contributor.author | Salguero-Jimenez, Alejandro | |
dc.contributor.author | Rodriguez San Pedro, Marcos Sintes | |
dc.contributor.author | Tiurma, Shindi | |
dc.contributor.author | McCutcheon, Lauren | |
dc.contributor.author | Gilmore, Adam | |
dc.contributor.author | de La Pompa, Jose Luis | |
dc.contributor.author | Chaudhry, Bill | |
dc.contributor.author | Henderson, Deborah J. | |
dc.date.accessioned | 2018-11-05T11:58:21Z | |
dc.date.available | 2018-11-05T11:58:21Z | |
dc.date.issued | 2018 | |
dc.identifier | ISI:000436921100001 | |
dc.identifier.citation | Elife. 2018; 7:e34110 | |
dc.identifier.issn | 2050-084X | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/6573 | |
dc.description.abstract | Abnormalities of the arterial valve leaflets, predominantly bicuspid aortic valve, are the commonest congenital malformations. Although many studies have investigated the development of the arterial valves, it has been assumed that, as with the atrioventricular valves, endocardial to mesenchymal transition (EndMT) is the predominant mechanism. We show that arterial is distinctly different from atrioventricular valve formation. Whilst the four septal valve leaflets are dominated by NCC and EndMT-derived cells, the intercalated leaflets differentiate directly from Tnnt2-Cre+/Isl1+ progenitors in the outflow wall, via a Notch-Jag dependent mechanism. Further, when this novel group of progenitors are disrupted, development of the intercalated leaflets is disrupted, resulting in leaflet dysplasia and bicuspid valves without raphe, most commonly affecting the aortic valve. This study thus overturns the dogma that heart valves are formed principally by EndMT, identifies a new source of valve interstitial cells, and provides a novel mechanism for causation of bicuspid aortic valves without raphe. | |
dc.description.sponsorship | British Heart Foundation RG/12/15/29935 Lorriane Eley Rachel V Richardson Lindsay Murphy Bill Chaudhry Deborah J Henderson; British Heart Foundation PG/15/46/31589 Lorriane Eley Bill Chaudhry Deborah J Henderson; Ministerio de Ciencia, Innovacion y Universidades of Spain CB16/11/00399 (Ciber Cardiovascular) Donal MacGrogan Alejandro Salguero-Jimenez Jose Luis de La Pompa; Ministerio de Ciencia, Innovacion y Universidades of Spain SAF2016-78370-R Donal MacGrogan Alejandro Salguero-Jimenez Jose Luis de La Pompa; Ministerio de Ciencia, Innovacion y Universidades of Spain RD16/0011/0021 (Red de Terapia Celular, TERCEL) Donal MacGrogan Alejandro Salguero-Jimenez Jose Luis de La Pompa; The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. | |
dc.language.iso | eng | |
dc.publisher | eLife Sciences Publications | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | 2ND HEART FIELD | |
dc.subject | HUMAN EMBRYONIC HEART | |
dc.subject | CARDIAC NEURAL CREST | |
dc.subject | OUTFLOW TRACT | |
dc.subject | SMOOTH-MUSCLE | |
dc.subject | MOUSE HEART | |
dc.subject | CARDIOVASCULAR DEVELOPMENT | |
dc.subject | ENDOCARDIAL CUSHIONS | |
dc.subject | EXPRESSION PATTERNS | |
dc.subject | SEMILUNAR VALVES | |
dc.title | A novel source of arterial valve cell linked to bicuspid aortic valve without rephe in mice | |
dc.type | journal article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 29956664 | |
dc.format.volume | 7 | |
dc.identifier.doi | 10.7554/eLife.34110 | |
dc.contributor.funder | British Heart Foundation | |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | |
dc.description.peerreviewed | Sí | |
dc.relation.publisherversion | https://doi.org/10.7554/eLife.34110 | |
dc.identifier.journal | eLife | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Señalización Intercelular durante el Desarrollo y la Enfermedad Cardiovascular | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2016-78370-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RD16/0011/0021 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/CB16/11/00399 | es_ES |