Conditional inactivation of Foxc1 and Foxc2 in neural crest cells leads to cardiac abnormalities.
Conditional inactivation of Foxc1 and Foxc2 in neural crest cells leads to cardiac abnormalities.
复制标题
神经嵴细胞中 Foxc1 和 Foxc2 的条件性失活会导致心脏异常。
DOI：
10.1002/dvg.23364
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Kume,Tsutomu
中科院分区：
文献类型：
--
作者：
Sanchez,Joshua;Miyake,Risa;Cheng,Andrew;Liu,Ting;Iseki,Sachiko;Kume,Tsutomu
心脏神经嵴细胞（cNCC）是心脏正常发育所必需的。cNCC是分化成多种细胞类型的多能和迁移细胞谱系。cNCC迁移到发育中的心脏中以促进心脏流出道（OFT）的分隔。Foxc 1和Foxc 2是FOX（Forkheadbox）转录因子家族的密切相关的成员，并且在心脏发育期间在cNCC中表达。然而，Foxc 1和Foxc 2在cNCC中的确切作用尚未完全描述。我们发现复合NCC特异性Foxc 1; Foxc 2突变胚胎表现出持续性动脉干（PTA）、室间隔缺损（VSD）和心室肌变薄。cNCC中Foxc 1/c2表达的缺失导致cNCC迁移到OFT中的异常模式，而不形成前房间隔。此外，cNCC中Foxc 1表达的缺失导致正常的OFT发育，但异常的室间隔形成。相比之下，在NCC中Foxc 2表达的缺失没有导致明显的心脏异常。总之，我们提供的证据表明，cNCC中的Foxc 1和Foxc 2是cNCC适当迁移、OFT分隔形成和心室发育所需的。我们的数据还表明，Foxc 1表达可能发挥更大的作用，在心室发育相比Foxc 2。
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 (Forkheadbox) 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‐specificFoxc1;Foxc2mutant embryos exhibited persistent truncus arteriosus (PTA), ventricular septal defects (VSDs), and thinning of the ventricular myocardium. Loss ofFoxc1/c2expression in cNCCs resulted in abnormal patterns of cNCC migration into the OFT without the formation of the aorticopulmonary septum. Further, loss ofFoxc1expression in cNCCs resulted in normal OFT development but abnormal ventricular septal formation. In contrast, loss ofFoxc2expression 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 thatFoxc1expression may play a larger role in ventricular development compared toFoxc2.