title: The development and maintenance of the mononuclear phagocyte system of the chick is controlled by signals from the macrophage colony-stimulating factor receptor.
abstract: BACKGROUND
  Macrophages have many functions in development and homeostasis as well as innate immunity. Recent studies in mammals suggest that cells arising in the yolk sac give rise to self-renewing macrophage populations that persist in adult tissues. Macrophage proliferation and differentiation is controlled by macrophage colony-stimulating factor (CSF1) and interleukin 34 (IL34), both agonists of the CSF1 receptor (CSF1R). In the current manuscript we describe the origin, function and regulation of macrophages, and the role of CSF1R signaling during embryonic development, using the chick as a model.
  
  
  RESULTS
  Based upon RNA-sequencing comparison to bone marrow-derived macrophages grown in CSF1, we show that embryonic macrophages contribute around 2% of the total embryo RNA in day 7 chick embryos, and have similar gene expression profiles to bone marrow-derived macrophages. To explore the origins of embryonic and adult macrophages, we injected Hamburger-Hamilton stage 16 to 17 chick embryos with either yolk sac-derived blood cells, or bone marrow cells from EGFP+ donors. In both cases, the transferred cells gave rise to large numbers of EGFP+ tissue macrophages in the embryo. In the case of the yolk sac, these cells were not retained in hatched birds. Conversely, bone marrow EGFP+ cells gave rise to tissue macrophages in all organs of adult birds, and regenerated CSF1-responsive marrow macrophage progenitors. Surprisingly, they did not contribute to any other hematopoietic lineage. To explore the role of CSF1 further, we injected embryonic or hatchling CSF1R-reporter transgenic birds with a novel chicken CSF1-Fc conjugate. In both cases, the treatment produced a large increase in macrophage numbers in all tissues examined. There were no apparent adverse effects of chicken CSF1-Fc on embryonic or post-hatch development, but there was an unexpected increase in bone density in the treated hatchlings.
  
  
  CONCLUSIONS
  The data indicate that the yolk sac is not the major source of macrophages in adult birds, and that there is a macrophage-restricted, self-renewing progenitor cell in bone marrow. CSF1R is demonstrated to be limiting for macrophage development during development in ovo and post-hatch. The chicken provides a novel and tractable model to study the development of the mononuclear phagocyte system and CSF1R signaling.
authors: Valerie
authors: V
authors: Garceau
authors: Adam
authors: A
authors: Balic
authors: Carla
authors: C
authors: Garcia-Morales
authors: Kristin A
authors: KA
authors: Sauter
authors: Mike J
authors: MJ
authors: McGrew
authors: Jacqueline
authors: J
authors: Smith
authors: Lonneke
authors: L
authors: Vervelde
authors: Adrian
authors: A
authors: Sherman
authors: Troy E
authors: TE
authors: Fuller
authors: Theodore
authors: T
authors: Oliphant
authors: John A
authors: JA
authors: Shelley
authors: Raksha
authors: R
authors: Tiwari
authors: Thomas L
authors: TL
authors: Wilson
authors: Cosmin
authors: C
authors: Chintoan-Uta
authors: Dave W
authors: DW
authors: Burt
authors: Mark P
authors: MP
authors: Stevens
authors: Helen M
authors: HM
authors: Sang
authors: David A
authors: DA
authors: Hume
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D012157:Mononuclear Phagocyte System / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000187:drug effects; D015017:Yolk Sac / Q000166:cytology
chemical_list: D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor