Department of Pediatrics, CRI Developmental Vascular Biology Program, Translational and Biomedical Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
PLoS One. 2011 Feb 25;6(2):e14732. doi: 10.1371/journal.pone.0014732.
Vasculogenesis, the de novo formation of blood vessels from precursor cells is critical for a developing embryo. However, the signals and events that dictate the formation of primary axial vessels remain poorly understood.
METHODOLOGY/PRINCIPAL FINDINGS: In this study, we use ets-related protein-1 (etsrp), which is essential for vascular development, to analyze the early stages of vasculogenesis in zebrafish. We found etsrp(+) cells of the head, trunk and tail follow distinct developmental sequences. Using a combination of genetic, molecular and chemical approaches, we demonstrate that fli(+)etsrp(+) hemato-vascular progenitors (FEVPs) are proliferating at the lateral plate mesoderm (LPM). The Shh-VEGF-Notch-Hey2 signaling pathway controls the proliferation process, and experimental modulation of single components of this pathway alters etsrp(+) cell numbers at the LPM.
CONCLUSIONS/SIGNIFICANCE: This study for the first time defines factors controlling proliferation, and cell numbers of pre-migratory FEVPs in zebrafish.
血管发生,即从前体细胞中新形成血管,对于胚胎的发育至关重要。然而,决定初级轴血管形成的信号和事件仍知之甚少。
方法/主要发现:在这项研究中,我们使用了对血管发育至关重要的 Ets 相关蛋白-1(etsrp),来分析斑马鱼血管发生的早期阶段。我们发现头部、躯干和尾部的 etsrp(+)细胞遵循不同的发育序列。通过遗传、分子和化学方法的结合,我们证明 fli(+)etsrp(+) 造血血管祖细胞(FEVPs)在侧板中胚层(LPM)中增殖。Shh-VEGF-Notch-Hey2 信号通路控制着增殖过程,而该通路单个成分的实验调节会改变 LPM 中 etsrp(+)细胞的数量。
结论/意义:这项研究首次定义了控制斑马鱼前迁移 FEVPs 增殖和细胞数量的因素。