title: Expression and domain-specific function of GATA-2 during differentiation of the hematopoietic precursor cells in midgestation mouse embryos.
abstract: The aorta-gonads-mesonephros (AGM) region of the mouse embryo has been assigned as the origin of definitive hematopoiesis. The transcription factor GATA-2 has specific but unclarified roles in early hematopoiesis. To elucidate the expression profile of GATA-2, we prepared transgenic mouse lines containing the green fluorescent protein (GFP) gene driven by GATA-2 gene regulatory elements. We also prepared a mouse line in which GFP reporter sequences were inserted into the endogenous GATA-2 gene. Both mouse mutants expressed GFP in the early hematopoietic tissues. The CD45 antigen, a marker of hematopoietic cells, was expressed in a small fraction of transgene (TG)-derived GFP+ cells. The remaining TG-GFP+/CD45- cells were adherent to plastic and produced CD45+ hematopoietic cells abundantly when cultured in vitro. Exogenous expression of GATA-2 in TG-GFP+/CD45- cells from the AGM region inhibited their differentiation into CD45+ cells. Loss of GATA-2 function through the disruption of the GATA-2 locus enhanced the earlier emergence of CD45+ cells in the yolk sac of the 9.5-day conceptus. These results demonstrated that GATA-2 is expressed in the precursor of hematopoietic cells and works as a gatekeeper to preserve their immaturity. A reduction of GATA-2 expression or activity is required for the differentiation of precursors to hematopoietic cells.
authors.affiliation: Institute of Basic Medical Sciences, Tsukuba, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Minegishi
authors.forename: Norio
authors.initials: N
authors.lastname: Suzuki
authors.forename: Tomomasa
authors.initials: T
authors.lastname: Yokomizo
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Pan
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Nishikawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology*; D050989:GATA2 Transcription Factor; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; C494712:Gata2 protein, mouse; D008164:Luminescent Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens