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Published online before print January 5, 2010
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0909624

Received for publication September 18, 2009.
Revised November 24, 2009.
Accepted for publication November 28, 2009.

Article

Pivotal Advance: Avian colony-stimulating factor 1 (CSF-1), interleukin-34 (IL-34), and CSF-1 receptor genes and gene products

Valerie Garceau *, Jacqueline Smith *, Ian R. Paton *, Megan Davey *, Mario A. Fares {dagger}, David P. Sester *, David W. Burt *, and David A. Hume *@

*The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, United Kingdom; and{dagger}The Smurfit Institute of Genetics, Trinity College, University of Dublin, Dublin, Ireland

@ To whom correspondence should be addressed. E-mail: david.hume{at}roslin.ed.ac.uk.


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Abstract

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 CSF-1R. 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.

Key Words: chicken • zebra finch • macrophage • co-evolution