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.
Shmukler, Boris EHuston, Nicholas CThon, Jonathan NNi, Chih-WenKourkoulis, GeorgeLawson, Nathan DPaw, Barry HAlper, Seth LengHL114719/HL/NHLBI NIH HHS/U54HL119145/HL/NHLBI NIH HHS/P01HL032262/HL/NHLBI NIH HHS/R01HL079266/HL/NHLBI NIH HHS/P01 HL032262/HL/NHLBI NIH HHS/R01 DK070838/DK/NIDDK NIH HHS/R01DK070838/DK/NIDDK NIH HHS/LetterResearch Support, N.I.H., ExtramuralItaly2015/08/22 06:00Haematologica. 2015 Dec;100(12):e483-5. doi: 10.3324/haematol.2015.132449. Epub 2015 Aug 20.