Hematopoietic stem cells are an important population of cells that continuously produce and replace all blood and immune system cells throughout life. These rare cells are responsible for the curative effects of bone marrow transplants, which are used to treat a variety of conditions including many forms of blood cancer. Understanding how hematopoietic stem cells are made during embryonic development is important because it could teach us how to make such cells in the laboratory, and possibly allow circumvention of donor immune compatibility issues. In this research we describe a previously unknown set of molecular inputs that are required to make hematopoietic stem cells during embryonic development. Of note, this signaling pathway is required for environmental instruction of hematopoietic stem cells, meaning we are one step closer to understanding how to generate them in vitro. Eventually these findings may help us discover the complete set of molecular controls necessary for making hematopoietic stem cells.