Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77025, USA.
Dev Dyn. 2013 Jun;242(6):738-51. doi: 10.1002/dvdy.23956. Epub 2013 Apr 24.
During embryonic development, endothelial precursor cells (angioblasts) migrate relatively long distances to form the primary vascular plexus. The migratory behavior of angioblasts and localization of the primitive blood vessels is tightly regulated by pro-angiogenic and anti-angiogenic factors encountered in the embryonic environment. Despite the importance of corneal avascularity to proper vision, it is not known when avascularity is established in the developing cornea and how pro- and anti-angiogenic factors regulate this process.
Using Tg(tie1:H2B:eYFP) transgenic quail embryos to visualize fluorescently labeled angioblasts, we show that the presumptive cornea remains avascular despite the invasion of cells from the periocular region where migratory angioblasts reside and form the primary vasculature. Semiquantitative reverse transcriptase polymerase chain reaction analysis and spatiotemporal examination of gene expression revealed that pro- and anti-angiogenic factors were expressed in patterns indicating their potential roles in angioblast guidance.
Our findings show for the first time that chick corneal avascularity is established and maintained during development as the periocular vasculature forms. We also identify potential candidate pro- and anti-angiogenic factors that may play crucial roles during vascular patterning in the anterior eye.
在胚胎发育过程中,内皮前体细胞(血管母细胞)迁移相对较长的距离以形成初级血管丛。血管母细胞的迁移行为和原始血管的定位受胚胎环境中遇到的促血管生成和抗血管生成因子的紧密调节。尽管角膜无血管对正常视力很重要,但尚不清楚在发育中的角膜中何时建立无血管状态,以及促血管生成和抗血管生成因子如何调节这一过程。
使用 Tg(tie1:H2B:eYFP) 转基因鹌鹑胚胎来可视化荧光标记的血管母细胞,我们表明,尽管来自眼周区域的细胞入侵并形成初级血管,但假定的角膜仍然保持无血管状态,在眼周区域中存在迁移的血管母细胞。半定量逆转录聚合酶链反应分析和时空基因表达检查显示,促血管生成和抗血管生成因子的表达模式表明它们在血管母细胞导向中可能发挥作用。
我们的研究结果首次表明,鸡角膜无血管状态是在眼周血管形成过程中建立和维持的。我们还确定了潜在的候选促血管生成和抗血管生成因子,它们可能在眼前部血管模式形成过程中发挥关键作用。