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A novel source of arterial valve cells linked to bicuspid aortic valve without raphe in mice

Lookup NU author(s): Dr Lorraine Eley, Dr Ahlam Alqahtani, Dr Rachel Richardson, Dr Lindsay Murphy, Shindi Tiurma, Lauren Mccutcheon, Adam Gilmore, Dr Bill Chaudhry, Professor Deborah HendersonORCiD



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.

Publication metadata

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

Journal: eLife

Year: 2018

Volume: 7

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


DOI: 10.7554/eLife.34110


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Funder referenceFunder name
PG/15/46/31589British Heart Foundation