Activation of Hematopoiesis and Vasculogenesis in the Mouse Embryo: Induction and Reprogramming of Ectodermal Cell Fate by Signals from Primitive Endoderm

During vertebrate gastrulation, the anterior-posterior axis of the embryo becomes morphologically evident, mesoderm is induced from ectoderm, and the basic body plan of the animal is established. Nascent mesoderm arises from the primitive streak, a structure which forms at the posterior pole of the embryo. The first mesodermal cell types to form are primitive erythroblasts and vascular endothelial cells, said to represent "posterior" cell fates. Using a novel transgenic explant culture system, we showed that development of these lineages is not mesoderm-autonomous but requires signals secreted from the adjacent primitive endoderm. Remarkably, these signals can also reprogram anterior embryonic ectoderm, a tissue that ordinarily would form neural structures, to form blood and endothelial cells. Therefore, primitive endoderm is a source of instructive signals for the activation of hematopoietic and vascular cell lineages and also plays a key role in anterior-posterior patterning of the mouse embryo.