title: The fractalkine receptor but not CCR2 is present on microglia from embryonic development throughout adulthood.
abstract: Microglial cells are difficult to track during development because of the lack of specific reagents for myeloid subpopulations. To further understand how myeloid lineages differentiate during development to create microglial cells, we investigated CX3CR1 and CCR2 transcription unit activation in Cx3cr1(+/GFP)CCR2(+/RFP) knockin fluorescent protein reporter mice. The principal findings include: 1) CX3CR1(+) cells localized to the aorta-gonad-mesonephros region, and visualized at embryonic day (E)9.0 in the yolk sac and neuroectoderm; 2) at E10.5, CX3CR1 single-positive microglial cells were visualized penetrating the neuroepithelium; and 3) CX3CR1 and CCR2 distinguished infiltrating macrophages from resident surveillant or activated microglia within tissue sections and by flow cytometric analyses. Our results support the contribution of the yolk sac as a source of microglial precursors. We provide a novel model to monitor chemokine receptor expression changes in microglia and myeloid cells early (E8.0-E10.5) in development and during inflammatory conditions, which have been challenging to visualize in mammalian tissues.
authors.affiliation: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Makiko
authors.initials: M
authors.lastname: Mizutani
authors.forename: Paula A
authors.initials: PA
authors.lastname: Pino
authors.forename: Noah
authors.initials: N
authors.lastname: Saederup
authors.forename: Israel F
authors.initials: IF
authors.lastname: Charo
authors.forename: Richard M
authors.initials: RM
authors.lastname: Ransohoff
authors.forename: Astrid E
authors.initials: AE
authors.lastname: Cardona
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D004622:Embryo, Mammalian / Q000196:embryology* / Q000276:immunology; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D009928:Organ Specificity / Q000502:physiology; D054390:Receptors, CCR2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515335:Ccr2 protein, mouse; C471885:Cx3cr1 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine
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