Cardiac neural crest cells (cNCCs) are required for normal heart development. cNCCs are a multipotent and migratory cell lineage that differentiates into multiple cell types. cNCCs migrate into the developing heart to contribute to the septation of the cardiac outflow tract (OFT). Foxc1 and Foxc2 are closely related members of the FOX (Forkhead box) transcription factor family and are expressed in cNCC during heart development. However, the precise role of Foxc1 and Foxc2 in cNCCs has yet to be fully described. We found that compound NCC‐specific Foxc1;Foxc2 mutant embryos exhibited persistent truncus arteriosus (PTA), ventricular septal defects (VSDs), and thinning of the ventricular myocardium. Loss of Foxc1/c2 expression in cNCCs resulted in abnormal patterns of cNCC migration into the OFT without the formation of the aorticopulmonary septum. Further, loss of Foxc1 expression in cNCCs resulted in normal OFT development but abnormal ventricular septal formation. In contrast, loss of Foxc2 expression in NCCs led to no obvious cardiac abnormalities. Together, we provide evidence that Foxc1 and Foxc2 in cNCCs are cooperatively required for proper cNCC migration, the formation of the OFT septation, and the development of the ventricles. Our data also suggests that Foxc1 expression may play a larger role in ventricular development compared to Foxc2.

中文翻译：

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神经c细胞中Foxc1和Foxc2的条件失活会导致心脏异常。

正常的心脏发育需要心脏神经c细胞（cNCC）。cNCC是一种能分化为多种细胞类型的多能迁移细胞系。cNCC迁移到发育中的心脏中，有助于分隔心脏流出道（OFT）。Foxc1和Foxc2是FOX（F orkhead b o x）转录因子家族的密切相关成员，在心脏发育过程中在cNCC中表达。但是，Foxc1和Foxc2在cNCC中的确切作用尚未完全描述。我们发现复合NCC特异性Foxc1; Foxc2突变体胚胎表现出持续性动脉瘤（PTA），室间隔缺损（VSD）和心室心肌变薄。Foxc1 / c2的损失cNCC中的表达导致cNCC迁移到OFT中的异常模式而没有形成主肺间隔。此外，cNCC中Foxc1表达的缺失导致正常的OFT发展，但异常的室间隔形成。相反，NCC中Foxc2表达的丧失不会导致明显的心脏异常。在一起，我们提供的证据表明，cNCC中的Foxc1和Foxc2是适当的cNCC迁移，OFT分隔的形成和心室发育的合作需要。我们的数据还表明，与Foxc2相比，Foxc1的表达在心室发育中可能发挥更大的作用。