The homeoprotein Hex is required for hemangioblast differentiation.

The first hematopoietic and endothelial progenitors are derived from a common embryonic precursor termed the hemangioblast. The genetic cascades that regulate the differentiation of the hemangioblast to hematopoietic and endothelial cells are largely unknown. In general, much of embryonic development is coordinately regulated by temporal and spatial expression of transcription factors, such as the Homeobox (Hox) gene family. We and others isolated a divergent homeobox gene termed Hex (or Prh) that is preferentially expressed in hematopoietic and endothelial cells. Using in vitro Hex-/- embryonic stem (ES) cell differentiation, in vivo yolk sac hematopoietic progenitor assays, and chimeric mouse analysis, we found that Hex is required for differentiation of the hemangioblast to definitive embryonic hematopoietic progenitors and to a lesser extent endothelial cells. Therefore, Hex is a novel regulator of hemangioblast differentiation to hematopoietic and endothelial cells.