Hematopoiesis is a key process that leads to the formation of all blood cell lineages from a specialized, multipotent cell, named the Hematopoietic Stem Cell (HSC). During development, the embryo produces several waves of hematopoiesis that produce specialized subsets of hematopoietic cells. Tissue interactions and cell signaling play an essential role in developmental hematopoiesis by allowing the formation of hematopoietic and endothelial cells (EC) from the mesoderm in particular in the yolk sac and by instructing the different generations of hematopoietic cells (HC). The embryonic aorta is another site wherein tissue interaction is essential for the production of the first HSCs that is achieved from a specialized subset of hemogenic endothelial cells. This production is tightly time-and space-controlled with the transcription factor Runx1 and the Notch signaling pathway playing a key role in this process and the surrounding tissues controlling the aortic shape and fate. Here we shall briefly review how hemogenic EC differentiate from the mesoderm, how the different aortic components assemble coordinately to establish the dorso-ventral polarity resulting in the initiation of Runx1 expression in hemogenic EC and the initiation of the hematopoietic program through modulation of the Notch-Runx1 axis. These data should help elucidate the first steps in HSC commitment and bring further insights into the manipulation of adult HSCs.