Odelin Gaëlle, Faure Emilie, Coulpier Fanny, Di Bonito Maria, Bajolle Fanny, Studer Michèle, Avierinos Jean-François, Charnay Patrick, Topilko Piotr, Zaffran Stéphane
Aix Marseille University, INSERM, GMGF, Marseille, France.
INSERM, U1024, IBENS, École normale supérieure, 46 rue d'Ulm, 75005 Paris, France.
Development. 2018 Jan 3;145(1):dev151944. doi: 10.1242/dev.151944.
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 function results in hyperplastic aortic valve and partially penetrant bicuspid aortic valve formation. Similar defects are observed in neural crest -deficient embryos. Genetic lineage tracing in 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 -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 in arterial valve development and reveal that an excess of neural crest cells may be associated with bicuspid aortic valve.
尽管心脏神经嵴细胞在动脉瓣发育的早期阶段是必需的，但其在瓣叶成熟过程中的作用仍知之甚少。在这里，我们在小鼠中发现，耳前和耳后区域的神经嵴细胞对动脉瓣叶有不同的贡献。对表达Krox20的神经嵴细胞进行基因命运图谱分析表明，其对动脉瓣的边界和瓣叶间三角区有很大贡献。功能丧失导致主动脉瓣增生和部分穿透性二叶主动脉瓣形成。在神经嵴缺陷胚胎中也观察到类似的缺陷。对突变小鼠进行基因谱系追踪表明，内皮衍生细胞正常，而神经嵴衍生细胞数量异常增加且在瓣叶中位置异常。相比之下，对表达细胞的基因消融不足以导致主动脉瓣缺陷，这表明相邻细胞可以补偿这种消耗。我们的研究结果证明了在动脉瓣发育中的关键作用，并揭示神经嵴细胞过多可能与二叶主动脉瓣有关。
