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Updated: Aug 28, 2025
Author Spotlight: Using Zebrafish to Explore Microglia Migration During Brain Development
Published on: May 17, 2024
Mafba and Mafbb regulate microglial colonization of zebrafish brain via controlling chemotaxis receptor expression
Abstract:
Microglia are the central nervous system (CNS)-resident macrophages involved in neural inflammation, neurogenesis, and neural activity regulation. Previous studies have shown that naturally occurring neuronal apoptosis plays a critical role in regulating microglial colonization of the brain in zebrafish. However, the molecular signaling cascades underlying neuronal apoptosis-mediated microglial colonization and the regulation of these cascades remain undefined. Here, we show that basic leucine zipper (b-Zip) transcription factors, Mafba and Mafbb, two zebrafish orthologs of mammalian MAFB, are key regulators in neuronal apoptosis-mediated microglial colonization of the brain in zebrafish. We document that the loss of Mafba and Mafbb function perturbs microglial colonization of the brain. We further demonstrate that Mafba and Mafbb act cell-autonomously and cooperatively to orchestrate microglial colonization, at least in part, by regulating the expression of G protein-coupled receptor 34a (Gpr34a), which directs peripheral macrophage recruitment into the brain through sensing the lysophosphatidylserine (lysoPS) released by the apoptotic neurons. Our study reveals that Mafba and Mafbb regulate neuronal apoptosis-mediated microglial colonization of the brain in zebrafish via the lysoPS-Gpr34a pathway.
Insights
Basic leucine zipper transcription factors Mafba and Mafbb regulate microglial colonization of the zebrafish brain. They control this process by orchestrating the lysophosphatidylserine-Gpr34a pathway, essential for brain macrophage recruitment.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia, the brain's resident macrophages, are crucial for CNS health, regulating inflammation, neurogenesis, and neural activity.
- Neuronal apoptosis (programmed cell death) is known to influence microglial colonization in the zebrafish brain.
- The precise molecular mechanisms driving apoptosis-mediated microglial brain entry remain largely unknown.
Purpose of the Study:
- To identify key molecular regulators of neuronal apoptosis-mediated microglial colonization in the zebrafish brain.
- To elucidate the signaling pathways involved in directing microglial brain entry during development.
Main Methods:
- Utilized zebrafish models to investigate the function of basic leucine zipper (b-Zip) transcription factors, Mafba and Mafbb.
- Examined the effects of Mafba and Mafbb loss-of-function on microglial colonization patterns.
- Investigated the role of G protein-coupled receptor 34a (Gpr34a) and lysophosphatidylserine (lysoPS) signaling in this process.
Main Results:
- Mafba and Mafbb were identified as critical regulators of microglial brain colonization in zebrafish.
- Loss of Mafba and Mafbb function significantly disrupted normal microglial colonization patterns.
- These transcription factors act cooperatively and cell-autonomously, partly by regulating Gpr34a expression.
- The lysoPS-Gpr34a pathway, activated by apoptotic neurons, is essential for directing peripheral macrophage recruitment into the brain.
Conclusions:
- Mafba and Mafbb are essential for orchestrating microglial colonization of the zebrafish brain.
- The study reveals a novel pathway involving Mafba, Mafbb, lysoPS, and Gpr34a that governs brain macrophage entry.
- This finding provides crucial insights into the molecular control of neuroinflammation and brain immune cell development.
