Krox20 defines a subpopulation of cardiac neural crest cells contributing to arterial valves and bicuspid aortic valve

Gaelle Odelin (1) , Emilie Faure (1) , Fanny Coulpier (2) , Maria Di Bonito (3) , Fanny Bajolle (4) , Michèle Studer (3) , Jean-François Avierinos (1) , Patrick Charnay (2) , Piotr Topilko (2) , Stéphane Zaffran (1)

1 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
2 IBENS - Institut de biologie de l'ENS Paris
3 IBV - Institut de Biologie Valrose
4 UPD5 - Université Paris Descartes - Paris 5

Although cardiac neural crest cells are required at early stages of arterial valve development, their contribution during valvular leaflet maturation remains poorly understood. Here, we show in mouse that neural crest cells from pre-otic and post-otic regions make distinct contributions to the arterial valve leaflets. Genetic fate-mapping analysis of Krox20-expressing neural crest cells shows a large contribution to the borders and the interleaflet triangles of the arterial valves. Loss of Krox20 function results in hyperplastic aortic valve and partially penetrant bicuspid aortic valve formation. Similar defects are observed in neural crest Krox20-deficient embryos. Genetic lineage tracing in Krox20(-/-) mutant mice shows that endothelial-derived cells are normal, whereas neural crest-derived cells are abnormally increased in number and misplaced in the valve leaflets. In contrast, genetic ablation of Krox20-expressing cells is not sufficient to cause an aortic valve defect, suggesting that adjacent cells can compensate this depletion. Our findings demonstrate a crucial role for Krox20 in arterial valve development and reveal that an excess of neural crest cells may be associated with bicuspid aortic valve.

Mots clés: Egr2; Bicuspid aortic valve; Cardiac development; Neural crest; Krox20; Mouse; Genetics

Domaines: Génétique

Gaelle Odelin, Emilie Faure, Fanny Coulpier, Maria Di Bonito, Fanny Bajolle, et al.. Krox20 defines a subpopulation of cardiac neural crest cells contributing to arterial valves and bicuspid aortic valve. Development (Cambridge, England), 2018, 145 (1), pp.dev151944. ⟨10.1242/dev.151944⟩. ⟨hal-01874792⟩