PUBLICATION

Differential Requirement for irf8 in Formation of Embryonic and Adult Macrophages in Zebrafish

Authors
Shiau, C.E., Kaufman, Z., Meireles, A.M., Talbot, W.S.
ID
ZDB-PUB-150124-3
Date
2015
Source
PLoS One   10: e0117513 (Journal)
Registered Authors
Shiau, Celia, Talbot, William S.
Keywords
none
MeSH Terms
  • Animals
  • Cells, Cultured
  • Gene Expression Regulation, Developmental
  • Interferon Regulatory Factors/genetics*
  • Interferon Regulatory Factors/metabolism*
  • Macrophages/metabolism*
  • Microglia/metabolism
  • Mutation
  • Myelopoiesis
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
25615614 Full text @ PLoS One
Abstract
Interferon regulatory factor 8 (Irf8) is critical for mammalian macrophage development and innate immunity, but its role in teleost myelopoiesis remains incompletely understood. In particular, genetic tools to analyze the role of Irf8 in zebrafish macrophage development at larval and adult stages are lacking. We generated irf8 null mutants in zebrafish using TALEN-mediated targeting. Our analysis defines different requirements for irf8 at different stages. irf8 is required for formation of all macrophages during primitive and transient definitive hematopoiesis, but not during adult-phase definitive hematopoiesis starting at 5-6 days postfertilization. At early stages, irf8 mutants have excess neutrophils and excess cell death in pu.1-expressing myeloid cells. Macrophage fates were recovered in irf8 mutants after wildtype irf8 expression in neutrophil and macrophage lineages, suggesting that irf8 regulates macrophage specification and survival. In juvenile irf8 mutant fish, mature macrophages are present, but at numbers significantly reduced compared to wildtype, indicating an ongoing requirement for irf8 after embryogenesis. As development progresses, tissue macrophages become apparent in zebrafish irf8 mutants, with the possible exception of microglia. Our study defines distinct requirement for irf8 in myelopoiesis before and after transition to the adult hematopoietic system.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping