Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Campus Gasthuisberg, Onderwijs & Navorsing 1, Herestraat 49, B-3000 Leuven, Belgium.
Biochem Biophys Res Commun. 2011 Jun 24;410(1):121-6. doi: 10.1016/j.bbrc.2011.05.117. Epub 2011 May 27.
Transcription factors play a central role in cell fate determination. Gene targeting in mice revealed that Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII, also known as Nuclear Receptor 2F2 or NR2F2) induces a venous phenotype in endothelial cells (ECs). More recently, NR2F2 was shown to be required for initiating the expression of Prox1, responsible for lymphatic commitment of venous ECs. Small animal models like zebrafish embryos and Xenopus laevis tadpoles have been very useful to elucidate mechanisms of (lymph) vascular development. Therefore, the role of NR2F2 in (lymph) vascular development was studied by eliminating its expression in these models. Like in mice, absence of NR2F2 in zebrafish resulted in distinct vascular defects including loss of venous marker expression, major trunk vessel fusion and vascular leakage. Both in zebrafish and Xenopus the development of the main lymphatic structures was severely hampered. NR2F2 knockdown significantly decreased prox1 expression in zebrafish ECs and the same manipulation affected lymphatic (L)EC commitment, migration and function in Xenopus tadpoles. Therefore, the role of NR2F2 in EC fate determination is evolutionary conserved.
转录因子在细胞命运决定中起着核心作用。在小鼠中的基因靶向研究表明，鸡卵清蛋白上游启动子转录因子 II（COUP-TFII，也称为核受体 2F2 或 NR2F2）在血管内皮细胞（ECs）中诱导静脉表型。最近，NR2F2 被证明是启动 Prox1 表达所必需的，Prox1 负责静脉 ECs 的淋巴管承诺。像斑马鱼胚胎和非洲爪蟾蝌蚪这样的小动物模型对于阐明（淋巴）血管发育的机制非常有用。因此，通过在这些模型中消除其表达，研究了 NR2F2 在（淋巴）血管发育中的作用。与在小鼠中一样，NR2F2 在斑马鱼中的缺失导致明显的血管缺陷，包括静脉标志物表达缺失、主要干线血管融合和血管渗漏。在斑马鱼和非洲爪蟾中，主要淋巴管结构的发育都受到严重阻碍。NR2F2 敲低显著降低了斑马鱼 ECs 中 prox1 的表达，并且相同的操作影响了非洲爪蟾蝌蚪的淋巴管（L）EC 承诺、迁移和功能。因此，NR2F2 在 EC 命运决定中的作用在进化上是保守的。
