Pivotal Advance: Avian colony-stimulating factor 1 (CSF-1), interleukin-34 (IL-34), and CSF-1 receptor genes and gene products.
Macrophages are involved in many aspects of development, host defense, pathology, and homeostasis. Their normal differentiation, proliferation, and survival are controlled by CSF-1 via the activation of the CSF1R. A recently discovered cytokine, IL-34, was shown to bind the same receptor in humans. Chicken is a widely used model organism in developmental biology, but the factors that control avian myelopoiesis have not been identified previously. The CSF-1, IL-34, and CSF1R genes in chicken and zebra finch were identified from respective genomic/cDNA sequence resources. Comparative analysis of the avian CSF1R loci revealed likely orthologs of mammalian macrophage-specific promoters and enhancers, and the CSF1R gene is expressed in the developing chick embryo in a pattern consistent with macrophage-specific expression. Chicken CSF-1 and IL-34 were expressed in HEK293 cells and shown to elicit macrophage growth from chicken BM cells in culture. Comparative sequence and co-evolution analysis across all vertebrates suggests that the two ligands interact with distinct regions of the CSF1R. These studies demonstrate that there are two separate ligands for a functional CSF1R across all vertebrates.
Garceau
Valerie
V
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, United Kingdom.
Smith
Jacqueline
J
Paton
Ian R
IR
Davey
Megan
M
Fares
Mario A
MA
Sester
David P
DP
Burt
David W
DW
Hume
David A
DA
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D001717:Birds; D002642:Chick Embryo; D002645:Chickens; D017124:Conserved Sequence; D046369:Finches; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D007378:Interleukins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D020836:Protein Structure, Quaternary; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
C529076:IL34 protein, human; D007378:Interleukins; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor