The gene regulatory network controlling the differentiation of developing HSC. (A) This diagram illustrates the position of hey2 within the gene regulatory network that controls arterial gene expression and HSC development during zebrafish embryogenesis. Genes shown in green are required for hey2 expression in the PLM at the 10s stage. Genes shown in blue are needed for maintenance of hey2 expression in the DA angioblast cord. Please note that our data neither clarify the position of individual Scl/Tal1 isoforms in the network relative to Hey2 nor provide insights into a specific late role of Scl/Tal1 in HSC formation. (B) This diagram illustrates whether or not runx1 expression can be rescued by activation of the Notch pathway in embryos that lack particular gene products. Loss of genes/gene products in green can be compensated by activation of the Notch pathway, whereas loss of genes/gene products in orange cannot. The diagram summarizes data from the present report and the literature.45 These data define a regulatory state, best described as early endothelial, that a cell needs to reach if it is to respond to a Notch signal by activating runx1 expression.