Related Experiment Video
Updated: May 21, 2026
Live Imaging and Characterization of Microglia Dynamics in the Zebrafish Embryo
Published on: May 17, 2024
Development of ramified microglia from early macrophages in the zebrafish optic tectum
Adam J Svahn1, Manuel B Graeber, Felix Ellett
1Brain and Mind Research Institute, Sydney Medical School, University of Sydney, 100 Mallett St., Camperdown, New South Wales 2050, Australia.
Abstract:
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. [2011]: Blood 117(4): e49-e56,). 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 postfertilization, 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 labeled highly branched cells in the skin overlying the optic tectum from 8-9 days postfertilization, 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.
Insights
Microglia develop from motile amoeboid cells into ramified cells in zebrafish larvae. This study visualizes microglia development and interactions in real-time, offering insights into brain immune cell dynamics.
Area of Science:
- Neuroimmunology
- Developmental Biology
- Cell Biology
Background:
- Microglia are essential brain-resident macrophages involved in homeostasis and immune responses.
- Understanding microglia development from primitive macrophages to mature forms is crucial.
- Previous studies lacked real-time assays for microglia morphological transitions.
Purpose of the Study:
- To develop a real-time assay for observing microglia development in vivo.
- To investigate the dynamic morphological changes and cellular interactions of developing microglia.
- To characterize the transition from early motile microglia to mature ramified forms.
Main Methods:
- Utilized zebrafish transgenic lines with fluorescent reporter expression driven by the macrophage expressed gene 1 (mpeg1) promoter.
- Observed microglia development in live, intact zebrafish larvae using in vivo imaging.
- Analyzed cell morphology, division, and interactions with other cells and vasculature.
Main Results:
- Demonstrated microglia originate from motile, phagocytic amoeboid cells.
- Showcased microglia rapidly transitioning between amoeboid and ramified shapes before settling into a mature morphology.
- Documented microglia interactions with brain capillaries and other microglia, including symmetric division up to 10 days postfertilization.
- Identified mpeg1-labeled cells in the skin as potential Langerhans cells.
Conclusions:
- The study provides the first real-time, high-resolution visualization of zebrafish microglia development.
- Established a novel assay for studying microglia dynamics in the intact brain.
- Revealed the dynamic morphing behavior and developmental trajectory of microglia.
- Highlighted the conserved nature of microglia morphology in zebrafish and mammals.
