PUBLICATION
In situ and transcriptomic identification of microglia in synapse-rich regions of the developing zebrafish brain
- Authors
- Silva, N.J., Dorman, L.C., Vainchtein, I.D., Horneck, N.C., Molofsky, A.V.
- ID
- ZDB-PUB-211010-2
- Date
- 2021
- Source
- Nature communications 12: 5916 (Journal)
- Registered Authors
- Molofsky, Anna Victoria
- Keywords
- none
- Datasets
- GEO:GSE164772, GEO:GSE164771
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Antigens, Differentiation, B-Lymphocyte/genetics
- Antigens, Differentiation, B-Lymphocyte/immunology
- Cathepsin B/genetics
- Cathepsin B/immunology
- Gene Expression Regulation, Developmental
- Genes, Reporter
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Histocompatibility Antigens Class II/genetics
- Histocompatibility Antigens Class II/immunology
- Mesencephalon/cytology*
- Mesencephalon/growth & development
- Mesencephalon/immunology
- Microglia/cytology*
- Microglia/immunology
- Neurogenesis/genetics*
- Neurogenesis/immunology
- Neurons/cytology
- Neurons/immunology
- Phagocytosis
- Rhombencephalon/cytology*
- Rhombencephalon/growth & development
- Rhombencephalon/immunology
- Single-Cell Analysis
- Superior Colliculi/cytology*
- Superior Colliculi/growth & development
- Superior Colliculi/immunology
- Synapses/immunology
- Synapses/metabolism
- Synapses/ultrastructure
- Transcriptome*
- Zebrafish
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/immunology
- PubMed
- 34625548 Full text @ Nat. Commun.
Citation
Silva, N.J., Dorman, L.C., Vainchtein, I.D., Horneck, N.C., Molofsky, A.V. (2021) In situ and transcriptomic identification of microglia in synapse-rich regions of the developing zebrafish brain. Nature communications. 12:5916.
Abstract
Microglia are brain resident macrophages that play vital roles in central nervous system (CNS) development, homeostasis, and pathology. Microglia both remodel synapses and engulf apoptotic cell corpses during development, but whether unique molecular programs regulate these distinct phagocytic functions is unknown. Here we identify a molecularly distinct microglial subset in the synapse rich regions of the zebrafish (Danio rerio) brain. We found that ramified microglia increased in synaptic regions of the midbrain and hindbrain between 7 and 28 days post fertilization. In contrast, microglia in the optic tectum were ameboid and clustered around neurogenic zones. Using single-cell mRNA sequencing combined with metadata from regional bulk sequencing, we identified synaptic-region associated microglia (SAMs) that were highly enriched in the hindbrain and expressed multiple candidate synapse modulating genes, including genes in the complement pathway. In contrast, neurogenic associated microglia (NAMs) were enriched in the optic tectum, had active cathepsin activity, and preferentially engulfed neuronal corpses. These data reveal that molecularly distinct phagocytic programs mediate synaptic remodeling and cell engulfment, and establish the zebrafish hindbrain as a model for investigating microglial-synapse interactions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping