Wilting Jörg, Tomarev Stanislav I, Christ Bodo, Schweigerer Lothar
Children's Hospital, Pediatrics I, University of Goettingen, Goettingen, Germany.
Lymphat Res Biol. 2003;1(1):33-40. doi: 10.1089/15396850360495673.
The origin of the lymphatic endothelium, either from the venous system or mesenchymal lymphangioblasts, presents as a persistent controversy. Recently, highly specific markers of the lymphatic endothelium have been found, enabling us to reinvestigate the embryonic origin of the lymphatics.
The homeobox transcription factor, Prox1, is expressed in lymphatic, but not in blood vascular, endothelial cells throughout murine and avian development and in adult human tissues. Here we show expression of scattered Prox1-positive cells in the dermatome of 4-day-old chick embryos by in situ hybridization and immunostaining. These cells obviously form the Prox1-positive lymphatic networks in the skin of the body wall and the limbs during further embryonic development. The Prox1 protein is localized in the nuclei of the lymphatic endothelial cells (LECs).
The results strongly suggest that the superficial lymphatics develop independently from the deep ones, and are derived from mesenchymal lymphangioblasts rather than veins. Our results argue against the unique origin of lymphatics from veins and suggest a heterogenous origin of LECs. The results are discussed in the context of historical data.
淋巴管内皮的起源,无论是来自静脉系统还是间充质淋巴管母细胞,一直存在争议。最近,已发现淋巴管内皮的高度特异性标志物,这使我们能够重新研究淋巴管的胚胎起源。
同源盒转录因子Prox1在整个小鼠和禽类发育过程以及成人组织中的淋巴管内皮细胞中表达,但在血管内皮细胞中不表达。在此,我们通过原位杂交和免疫染色显示,在4日龄鸡胚的生皮节中有散在的Prox1阳性细胞。在进一步的胚胎发育过程中,这些细胞明显在体壁和四肢皮肤中形成Prox1阳性淋巴管网络。Prox1蛋白定位于淋巴管内皮细胞(LECs)的细胞核中。
结果强烈表明,浅表淋巴管独立于深部淋巴管发育,且起源于间充质淋巴管母细胞而非静脉。我们的结果反对淋巴管起源于静脉的单一观点,并提示淋巴管内皮细胞起源具有异质性。我们结合历史数据对结果进行了讨论。