The AML1:CBFbeta transcription factor complex is essential for definitive hematopoiesis. Null mutations in mouse AML1 result in midgestational lethality with a complete lack of fetal liver hematopoiesis. While the cell autonomous nature and expression pattern of AML1 suggest an intrinsic role for this transcription factor in the developing hematopoietic system, no direct link to a functional cell type has been made. Here, we examine the consequences 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 spatial distribution of HSCs, leading to their early appearance in the normal position in the aorta-gonad-mesonephros region and also in the yolk sac.

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The aorta-gonad-mesonephros (AGM) region is a potent hematopoietic site in the midgestation mouse conceptus and first contains colony-forming units-spleen day 11 (CFU-S 11 ) at embryonic day 10 (E10). Because CFU-S 11 activity is present in the AGM region before the onset of hematopoietic stem cell (HSC) activity, CFU-S 11 activity in the complex developing vascular and urogenital regions of the AGM was localized. From E10 onward, CFU-S 11 activity is associated with the aortic vasculature, and is found also in the urogenital ridges (UGRs). Together with data obtained from organ explant cultures, in which up to a 16-fold increase in CFU-S 11 activity was observed, it was determined that CFU-S 11 can be increased autonomously both in vascular sites and in UGRs. Furthermore, CFU-S 11 activity is present in vitelline and umbilical vessels. This, together with the presence of CFU-S 11 in the UGRs 2 days before HSC activity, suggests both temporally and spatially distinct emergent sources of CFU-S 11 . (Blood. 2000;96:2902-2904)

The aorta-gonad-mesonephros (AGM) region is a potent hematopoietic site in the midgestation mouse conceptus and first contains colony-forming units–spleen day 11 (CFU-S11) at embryonic day 10 (E10). Because CFU-S11 activity is present in the AGM region before the onset of hematopoietic stem cell (HSC) activity, CFU-S11 activity in the complex developing vascular and urogenital regions of the AGM was localized. From E10 onward, CFU-S11 activity is associated with the aortic vasculature, and is found also in the urogenital ridges (UGRs). Together with data obtained from organ explant cultures, in which up to a 16-fold increase in CFU-S11 activity was observed, it was determined that CFU-S11 can be increased autonomously both in vascular sites and in UGRs. Furthermore, CFU-S11 activity is present in vitelline and umbilical vessels. This, together with the presence of CFU-S11 in the UGRs 2 days before HSC activity, suggests both temporally and spatially distinct emergent sources of CFU-S11.