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A novel source of arterial valve cells linked to bicuspid aortic valve without raphe in mice
Open accessAbstract
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.
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Metadata
- Authors
- Eley, L., Alqahtani, A. M., MacGrogan, D., Richardson, R. V., Murphy, L., Salguero-Jimenez, A., Sintes Rodriguez San Pedro, M., Tiurma, S., McCutcheon, L., Gilmore, A., de La Pompa, J. L., Chaudhry, B., & Henderson, D. J.
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2018-06-29
- Volume
- 7
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W2810440784
- Cited by
- 1,138
- References
- 9
- FWCI
- 43.08
- Type
- journal article
- Language
- en
- Open access
- gold
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