title: Differentiation of the mononuclear phagocyte system during mouse embryogenesis: the role of transcription factor PU.1.
abstract: During mouse embryogenesis, macrophage-like cells arise first in the yolk sac and are produced subsequently in the liver. The onset of liver hematopoiesis is associated with the transition from primitive to definitive erythrocyte production. This report addresses the hypothesis that a similar transition in phenotype occurs in myelopoiesis. We have used whole mount in situ hybridization to detect macrophage-specific genes expressed during mouse development. The mouse c-fms mRNA, encoding the receptor for macrophage colony-stimulating factor (CSF-1), was expressed on phagocytic cells in the yolk sac and throughout the embryo before the onset of liver hematopoiesis. Similar cells were detected using the mannose receptor, the complement receptor (CR3), or the Microphthalmia transcription factor (MITF) as mRNA markers. By contrast, other markers including the F4/80 antigen, the macrophage scavenger receptor, the S-100 proteins, S100A8 and S100A9, and the secretory product lysozyme appeared later in development and appeared restricted to only a subset of c-fms-positive cells. Two-color immunolabeling on disaggregated cells confirmed that CR3 and c-fms proteins are expressed on the same cells. Among the genes appearing later in development was the macrophage-restricted transcription factor, PU.1, which has been shown to be required for normal adult myelopoiesis. Mice with null mutations in PU.1 had normal numbers of c-fms-positive phagocytes at 11.5dpc. PU.1(-/-) embryonic stem cells were able to give rise to macrophage-like cells after cultivation in vitro. The results support previous evidence that yolk sac-derived fetal phagocytes are functionally distinct from those arising in the liver and develop via a different pathway.
authors.affiliation: Department of Microbiology and Centre for Molecular and Cellular Biology, University of Queensland, Queensland, Australia.
authors.forename: A M
authors.initials: AM
authors.lastname: Lichanska
authors.forename: C M
authors.initials: CM
authors.lastname: Browne
authors.forename: G W
authors.initials: GW
authors.lastname: Henkel
authors.forename: K M
authors.initials: KM
authors.lastname: Murphy
authors.forename: M C
authors.initials: MC
authors.lastname: Ostrowski
authors.forename: S R
authors.initials: SR
authors.lastname: McKercher
authors.forename: R A
authors.initials: RA
authors.lastname: Maki
authors.forename: D A
authors.initials: DA
authors.lastname: Hume
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen / Q000235:genetics; D008264:Macrophages / Q000166:cytology* / Q000502:physiology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D004268:DNA-Binding Proteins; D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051739:Microphthalmia-Associated Transcription Factor; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016186:Receptor, Macrophage Colony-Stimulating Factor; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C497235:Mitf protein, mouse