McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA.
Dev Cell. 2013 Apr 29;25(2):132-43. doi: 10.1016/j.devcel.2013.03.003.
The formation of the vascular system is essential for embryonic development and homeostasis. However, transcriptional control of this process is not fully understood. Here we report an evolutionarily conserved role for the transcription factor CASZ1 (CASTOR) in blood vessel assembly and morphogenesis. In the absence of CASZ1, Xenopus embryos fail to develop a branched and lumenized vascular system, and CASZ1-depleted human endothelial cells display dramatic alterations in adhesion, morphology, and sprouting. Mechanistically, we show that CASZ1 directly regulates Epidermal Growth Factor-Like Domain 7 (Egfl7). We further demonstrate that defects of CASZ1- or EGFL7-depleted cells are in part due to diminished RhoA expression and impaired focal adhesion localization. Moreover, these abnormal endothelial cell behaviors in CASZ1-depleted cells can be rescued by restoration of Egfl7. Collectively, these studies show that CASZ1 is required to directly regulate an EGFL7/RhoA-mediated pathway to promote vertebrate vascular development.
血管系统的形成对于胚胎发育和内稳态至关重要。然而，这一过程的转录控制还不完全清楚。在这里，我们报告了转录因子 CASZ1（CASTOR）在血管组装和形态发生中的一个进化保守作用。在 CASZ1 缺失的情况下，非洲爪蟾胚胎不能发育出分支和有腔的血管系统，而 CASZ1 耗尽的人内皮细胞在黏附、形态和发芽方面显示出明显的改变。在机制上，我们表明 CASZ1 直接调节表皮生长因子样结构域 7（Egfl7）。我们进一步证明，CASZ1 或 EGFL7 耗尽细胞的缺陷部分是由于 RhoA 表达减少和焦点黏附定位受损所致。此外，CASZ1 耗尽细胞中这些异常的内皮细胞行为可以通过 Egfl7 的恢复来挽救。总之，这些研究表明，CASZ1 是直接调节 EGFL7/RhoA 介导的途径以促进脊椎动物血管发育所必需的。
