Egfl7 Is Differentially Expressed in Arteries and Veins during Retinal Vascular Development

The vasculature of the central nervous system (CNS) is composed of vascular endothelial and mural cells which interact closely with glial cells and neurons. The development of the CNS vascularisation is a unique process which requires the contribution of specific regulators in addition to the classical angiogenic factors. The egfl7 gene is mainly detected in endothelial cells during physiological and pathological angiogenesis. Egfl7 codes for a secreted protein which predominantly accumulates into the extracellular space where it controls vascular elastin deposition or the Notch pathway. Egfl7 is the host gene of the microRNA miR126 which is also expressed in endothelial cells and which plays major functions during blood vessel development. While the expression of egfl7 and that of miR126 were well described in endothelial cells during development, their pattern of expression during the establishment of the CNS vasculature is still unknown. By analysing the expression of egfl7 and miR126 during mouse retina vascularisation, we observed that while expression of miR126 is detected in all endothelia, egfl7 is initially expressed in all endothelial cells and then is progressively restricted to veins and to their neighbouring capillaries. The recruitment of mural cells around retina arteries coincides with the down-regulation of egfl7 in the arterial endothelial cells, suggesting that this recruitment could be involved in the loss of egfl7 expression in arteries. However, the expression pattern of egfl7 is similar when mural cell recruitment is prevented by the injection of a PDGFRβ blocking antibody, suggesting that vessel maturation is not responsible for egfl7 down-regulation in retinal arteries.中枢神经系统（CNS）的脉管系统由血管内皮细胞与壁细胞构成，这类细胞与神经胶质细胞及神经元紧密相互作用。中枢神经系统血管化的发育是一类独特的过程，除经典血管生成因子外，还需特定调控因子的参与。egfl7基因在生理及病理性血管生成过程中主要在内皮细胞中表达。egfl7编码一种分泌型蛋白，该蛋白主要聚集于细胞外间隙，通过此空间调控血管弹性蛋白沉积或Notch信号通路。egfl7是微小RNA（microRNA）miR126的宿主基因，后者同样在内皮细胞中表达，并在血管发育过程中发挥关键功能。尽管人们已对发育阶段内皮细胞内egfl7与miR126的表达特征进行了充分描述，但二者在中枢神经系统脉管系统建立过程中的表达模式仍不明确。通过分析小鼠视网膜血管化进程中egfl7与miR126的表达情况，我们观察到：miR126可在所有内皮细胞中被检测到，而egfl7最初在全部内皮细胞中均有表达，随后逐渐局限于静脉及其邻近毛细血管。视网膜动脉周围壁细胞的募集，与动脉内皮细胞内egfl7的表达下调相吻合，这提示该募集过程可能参与了动脉内egfl7表达的缺失。然而，当通过注射PDGFRβ阻断抗体阻断壁细胞募集时，egfl7的表达模式并未出现显著差异，这表明血管成熟并非视网膜动脉内egfl7表达下调的诱因。