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Updated: Mar 17, 2026
Author Spotlight: Using Zebrafish to Explore Microglia Migration During Brain Development
Published on: May 17, 2024
Microglia Colonization of Developing Zebrafish Midbrain Is Promoted by Apoptotic Neuron and Lysophosphatidylcholine
Jin Xu1, Tienan Wang1, Yi Wu1
1Division of Life Science, State Key Laboratory of Molecular Neuroscience and Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, P.R. China.
Abstract:
Microglia are CNS-resident macrophages and play important roles in neural development and function. However, how microglial precursors born in peripheral tissues colonize the CNS remains undefined. Using in vivo imaging and genetic manipulation of zebrafish, we showed that microglial precursors enter the optic tectum of the midbrain, where the majority of microglia reside during early development, via the lateral periphery between the eyes and brain and the ventral periphery of the brain in a circulation-independent manner. The colonization of the optic tectum by microglial precursors is dynamic and driven by apoptotic neuronal death, which occurs naturally in the midbrain during neurogenesis. We further show that lysophosphatidylcholine, a phospholipid known to be released from apoptotic cells, can promote microglial precursor entry into the brain via its cognate receptors grp132b. Our study reveals that microglia colonization of developing zebrafish midbrain is triggered by apoptotic neuronal death, possibly via releasing lysophosphatidylcholine.
Insights
Microglial precursors colonize the zebrafish brain via specific pathways, independent of circulation. Apoptotic neuronal death, possibly via lysophosphatidylcholine, drives this crucial microglia colonization process.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Microglia, the brain's resident immune cells, are vital for neural development and function.
- The precise mechanisms by which microglial precursors migrate from peripheral tissues to colonize the central nervous system (CNS) remain largely unknown.
Purpose of the Study:
- To elucidate the pathways and mechanisms governing microglial precursor colonization of the developing CNS.
- To investigate the role of neuronal apoptosis in guiding microglial precursor migration into the brain.
Main Methods:
- In vivo imaging and genetic manipulation in zebrafish models.
- Tracking microglial precursor migration routes and dynamics.
- Analyzing the influence of apoptotic neuronal death on colonization.
Main Results:
- Microglial precursors enter the zebrafish optic tectum via lateral and ventral brain peripheries, independent of blood circulation.
- Colonization is a dynamic process actively driven by naturally occurring apoptotic neuronal death during neurogenesis.
- Lysophosphatidylcholine, released by apoptotic cells, promotes microglial precursor brain entry via GPR132B receptors.
Conclusions:
- Microglial colonization of the developing zebrafish midbrain is initiated by signals from apoptotic neurons.
- Lysophosphatidylcholine acts as a chemoattractant, mediating microglial precursor entry into the CNS.
