Patterson Lucy J, Gering Martin, Patient Roger
Weatherall Institute of Molecular Medicine, Oxford University, John Radcliffe Hospital, Headington, Oxford, OX3 9DS, United Kingdom.
Blood. 2005 May 1;105(9):3502-11. doi: 10.1182/blood-2004-09-3547. Epub 2005 Jan 11.
Blood and endothelial cells arise in close association in developing embryos, possibly from a shared precursor, the hemangioblast, or as hemogenic endothelium. The transcription factor, Scl/Tal1 (stem cell leukemia protein), is essential for hematopoiesis but thought to be required only for remodeling of endothelium in mouse embryos. By contrast, it has been implicated in hemangioblast formation in embryoid bodies. To resolve the role of scl in endothelial development, we knocked down its synthesis in zebrafish embryos where early precursors and later phenotypes can be more easily monitored. With respect to blood, the zebrafish morphants phenocopied the mouse knockout and positioned scl in the genetic hierarchy. Importantly, endothelial development was also clearly disrupted. Dorsal aorta formation was substantially compromised and gene expression in the posterior cardinal vein was abnormal. We conclude that scl is especially critical for the development of arteries where adult hematopoietic stem cells emerge, implicating scl in the formation of hemogenic endothelium.
在发育中的胚胎中,血液和内皮细胞紧密相关地产生,可能源自共同的前体细胞——成血管细胞,或者作为造血内皮细胞产生。转录因子Scl/Tal1(干细胞白血病蛋白)对造血作用至关重要,但被认为仅对小鼠胚胎中的内皮重塑是必需的。相比之下,它与胚状体中的成血管细胞形成有关。为了解决Scl在内皮发育中的作用,我们在斑马鱼胚胎中敲低其合成,在斑马鱼胚胎中早期前体细胞和后期表型更容易被监测。关于血液,斑马鱼突变体模拟了小鼠基因敲除的表型,并确定了Scl在基因层级中的位置。重要的是,内皮发育也明显受到破坏。背主动脉的形成严重受损,后主静脉中的基因表达异常。我们得出结论,Scl对成年造血干细胞出现的动脉发育尤为关键,这表明Scl参与了造血内皮细胞的形成。