Development of ramified microglia from early macrophages in the zebrafish optic tectum

Svahn, A.J., Graeber, M.B., Ellett, F., Lieschke, G.J., Rinkwitz, S., Bennett, M.R., and Becker, T.S.
Developmental Neurobiology   73(1): 60-71 (Journal)
Registered Authors
Becker, Thomas S., Ellett, Felix, Lieschke, Graham J., Rinkwitz, Silke, Svahn, Adam
GFP, Myelopoiesis, myeloid cells, dendritic cells
MeSH Terms
  • Analysis of Variance
  • Animals
  • Animals, Genetically Modified
  • Annexin A5/metabolism
  • Apoptosis/genetics
  • Brain/cytology
  • Brain/embryology
  • Cell Count
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental/genetics
  • Green Fluorescent Proteins/genetics
  • Luminescent Proteins/genetics
  • Macrophages/physiology*
  • Membrane Proteins/genetics
  • Microglia/physiology*
  • Microscopy, Confocal
  • Phagocytes/physiology
  • Superior Colliculi*/cytology
  • Superior Colliculi*/embryology
  • Superior Colliculi*/growth & development
  • Time Factors
  • Zebrafish
  • Zebrafish Proteins/genetics
22648905 Full text @ Dev. Neurobiol.

Microglia, the resident macrophage precursors of the brain, are necessary for the maintenance of tissue homeostasis and activated by a wide range of pathological stimuli. They have a key role in immune and inflammatory responses. Early microglia stem from primitive macrophages, however the transition from early motile forms to the ramified mature resident microglia has not been assayed in real time. In order to provide such an assay, we used zebrafish transgenic lines in which fluorescent reporter expression is driven by the promoter of macrophage expressed gene 1 (mpeg1; Ellet et al., Blood. 117(4):e49-56, 2011). This enabled the investigation of the development of these cells in live, intact larvae. We show that microglia develop from highly motile amoeboid cells that are engaged in phagocytosis of apoptotic cell bodies into a microglial cell type that rapidly morphs back and forth between amoeboid and ramified morphologies. These morphing microglia eventually settle into a typical mature ramified morphology. Developing microglia frequently come into contact with blood capillaries in the brain, and also frequently contact each other. Up to 10 days post fertilization, microglia were observed to undergo symmetric division. In the adult optic tectum, the microglia are highly branched, resembling mammalian microglia. In addition, the mpeg1 transgene also labelled highly branched cells in the skin overlying the optic tectum from 8-9 days post-fertilization, which likely represent Langerhans cells. Thus, the development of zebrafish microglia and their cellular interactions was studied in the intact developing brain in real time and at cellular resolution.

Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes