title: c-Maf plays a crucial role for the definitive erythropoiesis that accompanies erythroblastic island formation in the fetal liver.
abstract: c-Maf is one of the large Maf (musculoaponeurotic fibrosarcoma) transcription factors that belong to the activated protein-1 super family of basic leucine zipper proteins. Despite its overexpression in hematologic malignancies, the physiologic roles c-Maf plays in normal hematopoiesis have been largely unexplored. On a C57BL/6J background, c-Maf(-/-) embryos succumbed from severe erythropenia between embryonic day (E) 15 and E18. Flow cytometric analysis of fetal liver cells showed that the mature erythroid compartments were significantly reduced in c-Maf(-/-) embryos compared with c-Maf(+/+) littermates. Interestingly, the CFU assay indicated there was no significant difference between c-Maf(+/+) and c-Maf(-/-) fetal liver cells in erythroid colony counts. This result indicated that impaired definitive erythropoiesis in c-Maf(-/-) embryos is because of a non-cell-autonomous effect, suggesting a defective erythropoietic microenvironment in the fetal liver. As expected, the number of erythroblasts surrounding the macrophages in erythroblastic islands was significantly reduced in c-Maf(-/-) embryos. Moreover, decreased expression of VCAM-1 was observed in c-Maf(-/-) fetal liver macrophages. In conclusion, these results strongly suggest that c-Maf is crucial for definitive erythropoiesis in fetal liver, playing an important role in macrophages that constitute erythroblastic islands.
authors.affiliation: Department of Anatomy and Embryology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Kusakabe
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Michito
authors.initials: M
authors.lastname: Hamada
authors.forename: Megumi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohsumi
authors.forename: Hirona
authors.initials: H
authors.lastname: Suzuki
authors.forename: Mai Thi Nhu
authors.initials: MT
authors.lastname: Tran
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchida
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Ninomiya
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004622:Embryo, Mammalian; D004900:Erythroblasts / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D004920:Erythropoiesis / Q000235:genetics*; D005333:Fetus / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D008099:Liver / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D051257:Proto-Oncogene Proteins c-maf / Q000235:genetics / Q000502:physiology*
chemical_list: C495608:Maf protein, mouse; D051257:Proto-Oncogene Proteins c-maf