title: The AML1 transcription factor functions to develop and maintain hematogenic precursor cells in the embryonic aorta-gonad-mesonephros region.
abstract: We examined the role of the AML1 transcription factor in the development of hematopoiesis in the paraaortic splanchnopleural (P-Sp) and the aorta-gonad-mesonephros (AGM) regions of mouse embryos. The activity of colony-forming units of colonies from the P-Sp/AGM region was reduced severalfold by heterozygous 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 the AML1(+/+) genotype, both hematopoietic and endothelial-like cell types emerged, but in a culture of cells with the AML1(-/-) genotype, only endothelial-like cells emerged. Interestingly, introduction of AML1 cDNA into the P-Sp/AGM culture with the AML1(-/-) genotype partially restored the production of hematopoietic cells. This restoration was observed for cultures prepared from 9.5-day postcoitum (dpc) embryos but not for cultures prepared from 11.5-dpc embryos. Therefore, the population of endothelial-like cells capable 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 transcription factor functions to develop and maintain hematogenic precursor cells in the embryonic P-Sp/AGM region.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Mukouyama
authors.forename: N
authors.initials: N
authors.lastname: Chiba
authors.forename: T
authors.initials: T
authors.lastname: Hara
authors.forename: H
authors.initials: H
authors.lastname: Okada
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: R
authors.initials: R
authors.lastname: Kanamaru
authors.forename: A
authors.initials: A
authors.lastname: Miyajima
authors.forename: M
authors.initials: M
authors.lastname: Satake
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000196:embryology; D003114:Colony-Forming Units Assay; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D005260:Female; D018628:Gene Dosage; D018390:Gene Targeting; D005816:Genetic Complementation Test; D005838:Genotype; D006066:Gonads / Q000166:cytology / Q000196:embryology; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006579:Heterozygote; D008650:Mesonephros / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; C493726:Runx1 protein, mouse; D014157:Transcription Factors