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Blood, 12 March 2009, Vol. 113, No. 11, pp. 2535-2546.
Prepublished online as a Blood First Edition Paper on January 12, 2009; DOI 10.1182/blood-2008-07-171967.


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PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS

Zebrafish granulocyte colony-stimulating factor receptor signaling promotes myelopoiesis and myeloid cell migration

Clifford Liongue1,2, Chris J. Hall3, Bree A. O'Connell1,2, Phil Crosier3, and Alister C. Ward1

1 School of Medicine, Deakin University, Waurn Ponds, Australia; 2 Centre for Cellular and Molecular Biology, School of Life and Environmental Science, Deakin University, Burwood, Australia; and 3 Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand

Granulocyte colony-stimulating factor receptor (GCSFR) signaling participates in the production of neutrophilic granulocytes during normal hematopoietic development, with a particularly important role during emergency hematopoiesis. This study describes the characterization of the zebrafish gcsf and gcsfr genes, which showed broad conservation and similar regulation to their mammalian counterparts. Morpholino-mediated knockdown of gcsfr and overexpression of gcsf revealed the presence of an anterior population of myeloid cells during primitive hematopoiesis that was dependent on GCSF/GCSFR for development and migration. This contrasted with a posterior domain that was largely independent of this pathway. Definitive myelopoiesis was also partially dependent on a functional GCSF/GCSFR pathway. Injection of bacterial lipopolysaccharide elicited significant induction of gcsf expression and emergency production of myeloid cells, which was abrogated by gcsfr knockdown. Collectively, these data demonstrate GCSF/GCSFR to be a conserved signaling system for facilitating the production of multiple myeloid cell lineages in both homeostatic and emergency conditions, as well as for early myeloid cell migration, establishing a useful experimental platform for further dissection of this pathway.


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