Butko Emerald, Distel Martin, Pouget Claire, Weijts Bart, Kobayashi Isao, Ng Kevin, Mosimann Christian, Poulain Fabienne E, McPherson Adam, Ni Chih-Wen, Stachura David L, Del Cid Natasha, Espín-Palazón Raquel, Lawson Nathan D, Dorsky Richard, Clements Wilson K, Traver David
Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland.
Development. 2015 Mar 15;142(6):1050-61. doi: 10.1242/dev.119180.
The adult blood system is established by hematopoietic stem cells (HSCs), which arise during development from an endothelial-to-hematopoietic transition of cells comprising the floor of the dorsal aorta. Expression of aortic runx1 has served as an early marker of HSC commitment in the zebrafish embryo, but recent studies have suggested that HSC specification begins during the convergence of posterior lateral plate mesoderm (PLM), well before aorta formation and runx1 transcription. Further understanding of the earliest stages of HSC specification necessitates an earlier marker of hemogenic endothelium. Studies in mice have suggested that GATA2 might function at early stages within hemogenic endothelium. Two orthologs of Gata2 exist in zebrafish: gata2a and gata2b. Here, we report that gata2b expression initiates during the convergence of PLM, becoming restricted to emerging HSCs. We observe Notch-dependent gata2b expression within the hemogenic subcompartment of the dorsal aorta that is in turn required to initiate runx1 expression. Our results indicate that Gata2b functions within hemogenic endothelium from an early stage, whereas Gata2a functions more broadly throughout the vascular system.
成体血液系统由造血干细胞（HSCs）建立，造血干细胞在发育过程中由构成背主动脉底部的细胞从内皮向造血的转变产生。主动脉runx1的表达已作为斑马鱼胚胎中造血干细胞定向分化的早期标志物，但最近的研究表明，造血干细胞的特化始于后侧板中胚层（PLM）汇聚期间，远早于主动脉形成和runx1转录。对造血干细胞特化最早阶段的进一步了解需要一个更早的造血内皮标志物。小鼠研究表明，GATA2可能在造血内皮的早期阶段发挥作用。斑马鱼中有两个Gata2的直系同源基因：gata2a和gata2b。在此，我们报告gata2b的表达在PLM汇聚期间开始，并局限于新出现的造血干细胞。我们观察到背主动脉造血亚区中Notch依赖的gata2b表达，而这反过来又是启动runx1表达所必需的。我们的结果表明，Gata2b在造血内皮的早期阶段发挥作用，而Gata2a在整个血管系统中发挥更广泛的作用。
