Department of Medical Biophysics, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
PLoS One. 2013;8(1):e52197. doi: 10.1371/journal.pone.0052197. Epub 2013 Jan 14.
Lymphangiogenesis is a highly regulated process that involves the reprogramming of venous endothelial cells into early lymphatic endothelial cells. This reprogramming not only displays a polarized expression pattern from the cardinal vein, but also demonstrates vascular specificity; early lymphatics only develop from the cardinal vein and not the related dorsal aorta. In our transgenic model of lymphangiogenesis, we demonstrate that Prox1 overexpression has the ability to reprogram venous endothelium but not early arterial endothelial cells in vivo, in spite of the fact that Prox1 expression is forced onto both vascular beds. Our observations suggest that this specificity during embryogenesis may be due to cell-cell interactions between the developing arterial endothelial cells and smooth muscle cells. These conclusions have far reaching implications on how we understand the vascular specificity of lymphangiogenesis.
淋巴管生成是一个高度调控的过程,涉及将静脉内皮细胞重编程为早期淋巴管内皮细胞。这种重编程不仅表现出从心静脉的极化表达模式,而且还表现出血管特异性;早期淋巴管仅从心静脉而不是相关的背主动脉发育。在我们的淋巴管生成转基因模型中,我们证明了 Prox1 的过表达具有将静脉内皮细胞重编程为早期淋巴管内皮细胞的能力,但不能在体内将早期动脉内皮细胞重编程为早期淋巴管内皮细胞,尽管 Prox1 的表达被强制施加到两个血管床上。我们的观察结果表明,在胚胎发生过程中的这种特异性可能是由于发育中的动脉内皮细胞和平滑肌细胞之间的细胞-细胞相互作用所致。这些结论对于我们如何理解淋巴管生成的血管特异性具有深远的意义。