A novel source of arterial valve cells linked to bicuspid aortic valve without raphe in mice.
Elife
; 72018 06 29.
Article
em En
| MEDLINE
| ID: mdl-29956664
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Valva Aórtica
/
Células-Tronco
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Miócitos de Músculo Liso
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Células Epiteliais
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Receptor Notch1
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Proteína Jagged-1
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Doenças das Valvas Cardíacas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Elife
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Reino Unido