Haploinsufficiency of AML1 affects the temporal and spatial generation of hematopoietic stem cells in the mouse embryo

The AML1:CBF beta transcription factor complex is essential for definitive hematopoiesis. Null mutations in mouse AML1 result in midgestational lethal ity with a complete lack of fetal liver hematopoiesis. While the cell auton omous nature and expression pattern of AML1 suggest an intrinsic role for t his transcription factor in the developing hematopoietic system, no direct link to a functional cell type has been made. Here, we examine the conseque nces of AML1 loss in hematopoietic stem cells (HSC) of the mouse embryo. We demonstrate an absolute requirement for AML1 in functional HSCs. Moreover, haploinsufficiency results in a dramatic change in the temporal and spatia l distribution of HSCs, leading to their early appearance in the normal pos ition in the aorta-gonad-mesonephros region and also in the yolk sac.