PT  - JOURNAL ARTICLE
AU  - Nicholas J. Silva
AU  - Leah C. Dorman
AU  - Ilia D. Vainchtein
AU  - Nadine C. Horneck
AU  - Anna V. Molofsky
TI  - <em>In situ</em> and transcriptomic identification of synapse-associated microglia in the developing zebrafish brain
AID  - 10.1101/2021.05.08.443268
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.08.443268
4099  - http://biorxiv.org/content/early/2021/05/10/2021.05.08.443268.short
4100  - http://biorxiv.org/content/early/2021/05/10/2021.05.08.443268.full
AB  - 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 synapse-associated microglial subset in the zebrafish (Danio rerio). We found that ramified microglia populated synapse-rich 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 synapse-associated microglia (SAMs) that were highly enriched in the hindbrain, expressed known synapse modulating genes as well as novel candidates, and engulfed synaptic proteins. In contrast, neurogenic-associated microglia (NAMs) were enriched in optic tectum, had active cathepsin activity, and preferentially engulfed neuronal corpses. These data yielded a functionally annotated atlas of zebrafish microglia (https://www.annamolofskylab.org/microglia-sequencing). Furthermore, they reveal that molecularly distinct phagocytic programs mediate synaptic remodeling and cell engulfment, and establish zebrafish hindbrain as a model circuit for investigating microglial-synapse interactions.Competing Interest StatementThe authors have declared no competing interest.