Impaired embryonic haematopoiesis yet normal arterial development in the absence of the Notch ligand Jagged1
Impaired embryonic haematopoiesis yet normal arterial development in the absence of the Notch ligand Jagged1
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DOI：
10.1038/emboj.2008.113
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发表时间：
2008-07-09
期刊：
影响因子：
11.4
通讯作者：
Bigas, Anna
中科院分区：
文献类型：
--
作者：
Robert-Moreno, Alex;Guiu, Jordi;Bigas, Anna
Notch1和RBPjk在小鼠中的特异性缺失导致永久性造血的废除，伴随着胚胎阶段动脉身份的丧失。由于胚胎造血的产生可能需要事先进行动脉测定，因此很难确定Notch在这些突变体中的特异性造血作用。通过分析不同的Notch配体无效胚胎，我们现在表明，锯齿状蛋白1是不需要建立动脉命运，但它是正确执行明确的造血程序，包括GATA 2在背主动脉的表达所必需的。此外，通过用表达Jagged1的基质细胞或通过慢病毒介导的GATA2基因转导培养它们，获得了Jagged1无效AGM细胞的成功造血拯救。总之，我们的研究结果表明，锯齿状蛋白1介导的Notch1的激活是负责调节GATA 2的表达在AGM，这反过来又是必不可少的永久性造血在小鼠。
Specific deletion of Notch1 and RBPjk in the mouse results in abrogation of definitive haematopoiesis concomitant with the loss of arterial identity at embryonic stage. As prior arterial determination is likely to be required for the generation of embryonic haematopoiesis, it is difficult to establish the specific haematopoietic role of Notch in these mutants. By analysing different Notch-ligand-null embryos, we now show that Jagged1 is not required for the establishment of the arterial fate but it is required for the correct execution of the definitive haematopoietic programme, including expression of GATA2 in the dorsal aorta. Moreover, successful haematopoietic rescue of the Jagged1-null AGM cells was obtained by culturing them with Jagged1-expressing stromal cells or by lentiviral-mediated transduction of the GATA2 gene. Taken together, our results indicate that Jagged1-mediated activation of Notch1 is responsible for regulating GATA2 expression in the AGM, which in turn is essential for definitive haematopoiesis in the mouse.