The zebrafish ETS transcription factor Fli1b functions upstream of Scl/Tal1 during embryonic hematopoiesis.

During embryonic development, vascular endothelial and hematopoietic cells are thought to originate from a common precursor, the hemangioblast. The evolutionarily conserved ETS transcription factor FLI1 has been previously implicated in hemangioblast formation and hematopoietic and vascular development. However, its role in regulating the hemangioblast transition into hematovascular lineages is still incompletely understood. Its zebrafish paralog Fli1b (also known as Fli1rs) functions partially redundantly with the ETS transcription factor Etv2 (also known as Etsrp) during vasculogenesis and angiogenesis. However, its role in embryonic hematopoiesis has not been previously investigated. Here, we show that zebrafish fli1b mutants have a reduced formation of primitive erythrocytes and hematopoietic stem and progenitor cells, and display reduced expression of key regulators of hematopoiesis, including scl (also known as tal1), gata1a and runx1. Expression of scl was sufficient to partially rescue defects in erythroid differentiation in fli1b mutants, arguing that scl functions downstream of fli1b during primitive erythropoiesis. In addition, myelopoiesis was strongly misregulated in fli1b mutants. Although the formation of the earliest myeloid progenitors - neutrophils and macrophages - was greatly reduced in fli1b mutants, this was compensated by the increased emergence of myeloid cells from the alternative hematopoietic site - the endocardium. Intriguingly, myeloid cells in fli1b mutants retained vascular endothelial marker expression, suggesting that they are present in a hemangioblast-like state. In summary, our results demonstrate a novel role of fli1b transcription factor in regulating embryonic hematopoiesis.