Molecular regulation of embryonic hematopoiesis and vascular development: a novel pathway

In all vertebrate animals, the first blood and vascular endothelial cells are formed during gastrulation, a process in which the mesoderm of the embryo is induced and then patterned by molecules whose identity is still largely unknown. Clusters of developing blood cells surrounded by a layer of endothelial cells comprise the "blood islands" and form in the visceral yolk sac, external to the developing embryo proper. Despite the identification of genes, such as Flk1, SCL/tal-1, Cbfa2/Runx1/AML1, and CD34, that are expressed during the induction of primitive hematopoiesis and vasculogenesis, the early molecular and cellular events involved in these processes are not well understood. Recent work has demonstrated that extracellular signals secreted by a layer of visceral endoderm surrounding the embryo are essential for the initiation of these events. A member of the Hedgehog family of signaling molecules is produced by visceral endoderm and is required for formation of blood and endothelial cells in explant cultures. Hedgehog proteins also stimulate proliferation of definitive hematopoietic stem/progenitor cells. Therefore, these findings may have important medical implications for regulating hematopoiesis and vascular development for therapeutic purposes and for the development of new sources of hematopoietic stem cells for transplantation and as targets for gene therapy.