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Updated: Dec 13, 2025
Author Spotlight: Using Zebrafish to Explore Microglia Migration During Brain Development
Published on: May 17, 2024
Yolk sac-derived Pdcd11-positive cells modulate zebrafish microglia differentiation through the NF-κB-Tgfβ1 pathway
Ruimeng Yang1,2, Ming Zhan2,3, Miaomiao Guo2
1CNRS-LIA Hematology and Cancer, Sino-French Research Center for Life Sciences and Genomics, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, PR China.
Abstract:
Microglia are the primary immune cells in the central nervous system, which plays a vital role in neuron development and neurodegenerative diseases. Microglial precursors in peripheral hematopoietic tissues colonize the central nervous system during early embryogenesis. However, how intrinsic and extrinsic signals integrate to regulate microglia's differentiation remains undefined. In this study, we identified the cerebral white matter hyperintensities susceptibility gene, programmed cell death protein 11 (PDCD11), as an essential factor regulating microglia differentiation. In zebrafish, pdcd11 deficiency prevents the differentiation of the precursors to mature brain microglia. Although, the inflammatory featured macrophage brain colonization is augmented. At 22 h post fertilization, the Pdcd11-positive cells on the yolk sac are distinct from macrophages and neutrophils. Mechanistically, PDCD11 exerts its physiological role by differentially regulating the functions of nuclear factor-kappa B family members, P65 and c-Rel, suppressing P65-mediated expression of inflammatory cytokines, such as tnfα, and enhancing the c-Rel-dependent appearance of tgfβ1. The present study provides novel insights in understanding microglia differentiation during zebrafish development.
Insights
Programmed cell death protein 11 (PDCD11) is crucial for microglia differentiation in zebrafish. PDCD11 deficiency impairs microglia development while increasing inflammatory macrophage brain colonization.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia are key immune cells in the central nervous system, essential for neural development and implicated in neurodegenerative diseases.
- Microglial precursors originate in peripheral tissues and colonize the brain during embryogenesis.
- The precise regulation of microglia differentiation by intrinsic and extrinsic signals is not fully understood.
Purpose of the Study:
- To identify key regulators of microglia differentiation.
- To elucidate the role of programmed cell death protein 11 (PDCD11) in microglia development.
- To understand the molecular mechanisms by which PDCD11 influences immune cell populations in the brain.
Main Methods:
- Utilized zebrafish as a model organism to study microglia development.
- Investigated the effects of pdcd11 deficiency on microglial precursor differentiation and macrophage colonization.
- Analyzed the expression of inflammatory cytokines (tnfα) and growth factors (tgfβ1) in relation to PDCD11 function.
- Examined the differential regulation of nuclear factor-kappa B (NF-κB) family members, P65 and c-Rel.
Main Results:
- Identified PDCD11 as a critical gene for microglia differentiation in zebrafish.
- pdcd11 deficiency resulted in impaired differentiation of precursors into mature microglia.
- Inflammatory macrophage colonization of the brain was augmented in pdcd11-deficient zebrafish.
- PDCD11 was found to suppress P65-mediated inflammatory cytokine production while enhancing c-Rel-dependent tgfβ1 expression.
Conclusions:
- PDCD11 plays an essential role in regulating the differentiation of microglia from their precursors.
- The study reveals a novel mechanism involving PDCD11 in balancing inflammatory responses and promoting microglia maturation.
- These findings offer new insights into the developmental processes governing microglia populations in the brain.
