Zebrafish granulocyte colony-stimulating factor receptor signaling promotes myelopoiesis and myeloid cell migration.
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.
Liongue
Clifford
C
School of Medicine, Deakin University, Waurn Ponds, VIC, Australia.
Hall
Chris J
CJ
O'Connell
Bree A
BA
Crosier
Phil
P
Ward
Alister C
AC
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement / Q000235:genetics*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000378:metabolism / Q000502:physiology*; D023461:Myeloid Progenitor Cells / Q000378:metabolism / Q000502:physiology; D038042:Myelopoiesis / Q000235:genetics*; D010802:Phylogeny; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000502:physiology
D016188:Receptors, Granulocyte Colony-Stimulating Factor