Lookup NU author(s): Dr Lorraine Eley,
Dr Rachel Richardson,
Dr Lindsay Murphy,
Dr Bill Chaudhry,
Professor Deborah Henderson
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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.
Author(s): Eley L, Alqahtani A, MacGrogan D, Richardson R, Murphy L, Salguero-Jimenez A, Rodriguez San Pedro M, Tiurma S, McCutcheon L, Gilmore A, de La Pompa JL, Chaudhry B, Henderson D
Publication type: Article
Publication status: Published
Online publication date: 29/06/2018
Acceptance date: 12/06/2018
Date deposited: 19/07/2018
ISSN (electronic): 2050-084X
Publisher: eLife Sciences Publications Ltd
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