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转录因子Tbx18(Tbx18)在小鼠胚胎心外膜上皮细胞表达并调控心外膜上皮细胞向心系细胞分化.上皮间充质转化(EMT)过程是器官发育和形成的重要机制.为阐述Tbx18通过调控下游EMT关键信号分子参与心外膜上皮细胞分化和心脏发育,本研究运用Tbx18-Cre/Rosa26R-EYFP双杂合基因敲入小鼠和免疫荧光共聚焦,证实Tbx18+心系细胞和EMT关键信号分子Snail1、Smad、Slug、Twist在发育后期胚鼠心外膜和心外膜下间充质发生共聚焦.同时还发现,Tbx18在胚鼠不同发育阶段的表达模式和Tbx18+心系细胞内上述EMT关键信号分子的表达模式相似.Tbx18和EMT关键信号分子在发育心脏存在相似的时空表达模式,因此,它们之间可能存在相互调控作用.运用Tbx18突变技术揭示了Tbx18突变型胚鼠心脏EMT关键信号分子表达水平均较野生型显著下调,直接证实了上述4个EMT信号分子是Tbx18的可能靶点.理解Tbx18参与心脏发育的下游靶点有助于改善成年心脏损伤后的再生修复.
Transcription factor Tbx18 (Tbx18) is expressed in mouse embryonic epicardial epithelial cells and regulates epicardial epithelial cells towards cardiomyocytes. The process of epithelial mesenchymal transition (EMT) is an important mechanism of organ development and formation. In this study, Tbx18-Cre / Rosa26R-EYFP double-hybrid knock-in mice and immunofluorescence confocal microscopy were used to confirm the involvement of EMT key signaling molecules in epicardial cell differentiation and cardiac development. Signaling molecules Snail1, Smad, Slug, Twist confocal in the postnatal embryonic rat epicardial and epicardial mesenchyme confluence also found that Tbx18 expression pattern in different stages of embryonic mouse embryos and Tbx18 + The expression pattern of EMT key signal molecules is similar.The key signaling molecules ofTbx18 and EMT have similar spatial and temporal expression patterns in the developing heart.Therefore, there may exist mutual regulation between them.Using Tbx18 mutation technology revealed the key of EMT in Tbx18 mutant embryonic heart Signaling molecules were significantly downregulated compared with the wild type, directly confirmed the above four EMT signal molecules is a possible target Tbx18 understand Tbx18 involved in heart hair The downstream targets of fertilization help to improve the regeneration and repair of adult heart injury.