The development of vertebrate definitive hematopoiesis is featured by temporally and spatially dynamic distribution of hematopoietic stem/progenitor cells (HSPCs). It is proposed that the migration of definitive HSPCs, at least in part, accounts for this unique characteristic; however, compelling in vivo lineage evidence is still lacking. Here we present an in vivo analysis to delineate the migration route of definitive HSPCs in the early zebrafish embryo. Cell-marking analysis was able to first map definitive HSPCs to the ventral wall of dorsal aorta (DA). These cells were subsequently found to migrate to a previously unappreciated organ, posterior blood island (PBI), located between the caudal artery and caudal vein, and finally populate the kidney, the adult hematopoietic organ.
IntroductionThe ontogeny of vertebrate hematopoietic system is characterized by 2 phases of development: an early transitory primitive wave generating only primitive erythrocytes and some myeloid cells, and a definitive wave that initiates late and produces all the mature blood lineages (erythroid, myeloid, and lymphoid). [1][2][3][4] In vertebrates, the first hematopoietic activity can be identified in an extra-embryonic location: yolk sac in mice and chickens, or ventral blood island (VBI) in amphibians, leading to the hypothesis that yolk sac/VBI is the sole source of hematopoietic cells, which will in turn populate downstream hematopoietic compartments. 5 However, the singular hematopoietic origin from yolk sac/VBI is challenged by substantial evidence from experiments with various species that reveals another evolutionary conserved intraembryonic hematopoietic site: the para-aortic splanchnopleurae (pSP) and later referred as aorta-gonad-mesonephros (AGM). [6][7][8][9][10][11] Hence, it is currently believed that yolk sac/VBI mainly supports primitive hematopoiesis, whereas definitive hematopoiesis is autonomously initiated, at least in part, in the pSP/AGM region.The journey of definitive HSPCs is best characterized both temporally and spatially in mice. 4 Although multipotential hematopoietic progenitor cells revealed by in vitro colony assays, injection into yolk sac cavity, transplantation into fetal liver of newborn mice or reconstitution of immunodeficient mice, can be detected in the pSP/AGM region and yolk sac at earlier developmental stages, 12-15 the first definitive HSPCs, defined as cells fully competent to provide long-term reconstitution of irradiated adult recipients, emerge in the pSP/AGM region at embryonic day (E) 10.5. 6,9,11 Subsequently, at around E11.0, definitive HSPC activity can be found in yolk sac. 6,9,11 Recently, placenta is recognized as another embryonic reservoir from E10.5 for definitive HSPCs operation. 16,17 However, the cellular origin of definitive HSPCs in yolk sac and placenta and their contribution to adult hematopoiesis are not clear. From E11.5, fetal liver begins to be populated by definitive HSPCs and serves as the main site that supports hematopoietic expansion and differentiation dur...