Y. Mukouyama et al., The AML1 transcription factor functions to develop and maintain hematogenic precursor cells in the embryonic aorta-gonad-mesonephros region, DEVELOP BIO, 220(1), 2000, pp. 27-36
We examined the role of the AML1 transcription factor in the development of
hematopoiesis in the paraaortic splanchnopleural (P-Sp) and the aorta-gona
d-mesonephros (AGM) regions of mouse embryos. The activity of colony-formin
g units of colonies from the P-Sp/AGM region was reduced severalfold by het
erozygous disruption of the AML1 gene, indicating that AML1 functioned in a
dosage-dependent manner to generate hematopoietic progenitors. In addition
, no hematopoietic progenitor activity was detected in the P-Sp/AGM region
of embryos with an AML1 null mutation. Similar results were obtained when a
dispersed culture was first prepared from the P-Sp/AGM region before assay
of the activity of the colony-forming units. In a culture of cells with th
e AML1(+)(+) genotype, both hematopoietic and endothelial-like cell types e
merged, but in a culture of cells with the AML1(-/-) genotype, only endothe
lial-like cells emerged. Interestingly, introduction of AML1 cDNA into the
P-Sp/AGM culture with the AML1(-/-) genotype partially restored the product
ion of hematopoietic cells. This restoration was observed for cultures prep
ared from 9.5-day postcoitum (dpc) embryos but not for cultures prepared fr
om 11.5-dpc embryos. Therefore, the population of endothelial-like cells ca
pable of growing in the AML1(-/-) culture would appear to contain inert but
nonetheless competent hematogenic precursor cells up until at least the 9.
5-dpc period. All these results support the notion that the AML1 transcript
ion factor functions to develop and maintain hematogenic precursor cells in
the embryonic P-Sp/AGM region. (C) 2000 Academic Press.