Hirano Ikuo, Suzuki Norio
Department of Molecular Hematology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Division of Oxygen Biology, United Centers for Advanced Research and Translational Medicine, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Front Cell Dev Biol. 2019 Jun 12;7:105. doi: 10.3389/fcell.2019.00105. eCollection 2019.
While the neural crest is considered the fourth germ layer that originates a variety of tissues during mammalian development, we recently discovered that some neural crest cells and neuroepithelial cells play a unique role in secreting a vital hematopoietic hormone, erythropoietin (EPO), in mouse embryos. EPO production by the neural crest is transient in mid-stage embryos but essential for the first erythropoiesis in the yolk sac and for sufficient oxygen supply in the whole embryo growing . The site of EPO production shifts from the neural crest to the liver in late embryonic stages, followed by interstitial fibroblasts of the kidneys in adults. Interestingly, the transition of EPO production sites synchronizes with the transition of erythropoietic sites during mouse development from the yolk sac and the fetal liver to the bone marrow. EPO produced by the neural crest and the neuroepithelium is first stored around the production sites and delivered to the yolk sac as an endocrine hormone for erythropoiesis after heartbeat activation. The fact that EPO is produced by some human cell lines derived from neuroblastoma, which mainly originates from the neural crest, provides evidence that the neural crest secretes EPO for primitive erythropoiesis not only in mouse but also in human embryos. Here, we introduce and discuss recent progress in studies on the mechanism of EPO production by the neural crest and its roles in erythropoietic development and in the fate of EPO-producing neural crest cells.
虽然神经嵴被认为是在哺乳动物发育过程中产生多种组织的第四胚层，但我们最近发现，一些神经嵴细胞和神经上皮细胞在小鼠胚胎中分泌一种重要的造血激素——促红细胞生成素（EPO）方面发挥着独特作用。神经嵴产生的EPO在胚胎中期是短暂的，但对于卵黄囊中的首次红细胞生成以及整个生长胚胎的充足氧气供应至关重要。EPO的产生部位在胚胎后期从神经嵴转移到肝脏，在成年后则转移到肾脏的间质成纤维细胞。有趣的是，EPO产生部位的转变与小鼠发育过程中红细胞生成部位从卵黄囊和胎儿肝脏到骨髓的转变同步。神经嵴和神经上皮产生的EPO首先储存在产生部位周围，并在心跳激活后作为内分泌激素输送到卵黄囊用于红细胞生成。一些源自神经母细胞瘤（主要起源于神经嵴）的人类细胞系产生EPO这一事实表明，神经嵴不仅在小鼠胚胎中，而且在人类胚胎中都分泌EPO用于原始红细胞生成。在此，我们介绍并讨论了关于神经嵴产生EPO的机制及其在红细胞生成发育中的作用以及产生EPO的神经嵴细胞命运的研究进展。
