A role for Tbx5 in proepicardial cell migration during cardiogenesis
A role for Tbx5 in proepicardial cell migration during cardiogenesis
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DOI：
10.1152/physiolgenomics.00060.2004
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发表时间：
2004-07-08
影响因子：
4.6
通讯作者：
Basson, CT
中科院分区：
文献类型：
--
作者：
Hatcher, CJ;Diman, NYSG;Basson, CT
心外膜祖细胞在心外膜和冠状血管发育过程中的转录调控级联仍有待确定。我们使用人类胚胎组织的免疫组织化学证明TBX5转录因子不仅在心肌中表达，而且在整个胚胎心外膜和冠状脉管系统中表达。 TBX5 在其他人类胎儿血管床中不表达。此外，人类胚胎组织的免疫组织化学分析表明，与心外膜细胞不同，分层心外膜来源的细胞在进行冠状血管生成所需的上皮间质转化之前迁移穿过心外膜下层时不表达TBX5。在小鸡中，Tbx5 在胚胎心外膜前器官 (PEO) 中表达，该器官由心外膜和冠状血管祖细胞组成。逆转录病毒介导的人 TBX5 过度表达抑制受感染的心外膜细胞掺入新生鸡心外膜和冠状脉管系统。 TBX5 过表达以及反义介导的鸡 Tbx5 敲低会在 PEO 中产生细胞自主缺陷，从而阻止心外膜细胞迁移。因此，增加和减少Tbx5剂量都会损害心外膜的发育。外植 PEO 的培养表明，未经处理的鸡心外膜细胞在细胞迁移过程中下调 Tbx5 表达。因此，我们认为Tbx5参与心外膜细胞迁移的调节，这是心外膜和冠状脉管系统建立的关键事件。
Transcriptional regulatory cascades during epicardial and coronary vascular development from proepicardial progenitor cells remain to be defined. We have used immunohistochemistry of human embryonic tissues to demonstrate that the TBX5 transcription factor is expressed not only in the myocardium, but also throughout the embryonic epicardium and coronary vasculature. TBX5 is not expressed in other human fetal vascular beds. Furthermore, immunohistochemical analyses of human embryonic tissues reveals that unlike their epicardial counterparts, delaminating epicardial-derived cells do not express TBX5 as they migrate through the subepicardium before undergoing epithelial-mesenchymal transformation required for coronary vasculogenesis. In the chick, Tbx5 is expressed in the embryonic proepicardial organ (PEO), which is composed of the epicardial and coronary vascular progenitor cells. Retrovirus-mediated overexpression of human TBX5 inhibits cell incorporation of infected proepicardial cells into the nascent chick epicardium and coronary vasculature. TBX5 overexpression as well as antisense-mediated knockdown of chick Tbx5 produce a cell-autonomous defect in the PEO that prevents proepicardial cell migration. Thus, both increasing and decreasing Tbx5 dosage impairs development of the proepicardium. Culture of explanted PEOs demonstrates that untreated chick proepicardial cells downregulate Tbx5 expression during cell migration. Therefore, we propose that Tbx5 participates in regulation of proepicardial cell migration, a critical event in the establishment of the epicardium and coronary vasculature.