PMID- 34625548
OWN - NLM
STAT- MEDLINE
DCOM- 20211102
LR  - 20211102
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Oct 8
TI  - In situ and transcriptomic identification of microglia in synapse-rich regions of 
      the developing zebrafish brain.
PG  - 5916
LID - 10.1038/s41467-021-26206-x [doi]
LID - 5916
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 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.
CI  - (c) 2021. The Author(s).
FAU - Silva, Nicholas J
AU  - Silva NJ
AUID- ORCID: 0000-0001-5241-0034
AD  - Department of Psychiatry and Behavioral Sciences/Weill Institute for 
      Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
FAU - Dorman, Leah C
AU  - Dorman LC
AUID- ORCID: 0000-0002-5511-887X
AD  - Department of Psychiatry and Behavioral Sciences/Weill Institute for 
      Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
AD  - Neuroscience Graduate Program, University of California, San Francisco, San 
      Francisco, CA, USA.
FAU - Vainchtein, Ilia D
AU  - Vainchtein ID
AD  - Department of Psychiatry and Behavioral Sciences/Weill Institute for 
      Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
FAU - Horneck, Nadine C
AU  - Horneck NC
AUID- ORCID: 0000-0003-4941-6798
AD  - Department of Psychiatry and Behavioral Sciences/Weill Institute for 
      Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
FAU - Molofsky, Anna V
AU  - Molofsky AV
AUID- ORCID: 0000-0002-4709-2411
AD  - Department of Psychiatry and Behavioral Sciences/Weill Institute for 
      Neurosciences, University of California, San Francisco, San Francisco, CA, USA. 
      anna.molofsky@ucsf.edu.
AD  - Kavli Institute for Fundamental Neuroscience, University of California, San 
      Francisco, San Francisco, CA, USA. anna.molofsky@ucsf.edu.
LA  - eng
GR  - R01 MH119349/MH/NIMH NIH HHS/United States
GR  - DP2 MH116507/MH/NIMH NIH HHS/United States
GR  - K12 GM081266/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211008
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Antigens, Differentiation, B-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Zebrafish Proteins)
RN  - 0 (enhanced green fluorescent protein)
RN  - 0 (invariant chain)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 3.4.22.1 (Cathepsin B)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Antigens, Differentiation, B-Lymphocyte/genetics/immunology
MH  - Cathepsin B/genetics/immunology
MH  - Gene Expression Regulation, Developmental
MH  - Genes, Reporter
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Histocompatibility Antigens Class II/genetics/immunology
MH  - Mesencephalon/*cytology/growth & development/immunology
MH  - Microglia/*cytology/immunology
MH  - Neurogenesis/*genetics/immunology
MH  - Neurons/cytology/immunology
MH  - Phagocytosis
MH  - Rhombencephalon/*cytology/growth & development/immunology
MH  - Single-Cell Analysis
MH  - Superior Colliculi/*cytology/growth & development/immunology
MH  - Synapses/immunology/metabolism/ultrastructure
MH  - *Transcriptome
MH  - Zebrafish
MH  - Zebrafish Proteins/*genetics/immunology
PMC - PMC8501082
COIS- The authors declare no competing interests.
EDAT- 2021/10/10 06:00
MHDA- 2021/11/03 06:00
PMCR- 2021/10/08
CRDT- 2021/10/09 05:45
PHST- 2021/04/29 00:00 [received]
PHST- 2021/09/16 00:00 [accepted]
PHST- 2021/10/09 05:45 [entrez]
PHST- 2021/10/10 06:00 [pubmed]
PHST- 2021/11/03 06:00 [medline]
PHST- 2021/10/08 00:00 [pmc-release]
AID - 10.1038/s41467-021-26206-x [pii]
AID - 26206 [pii]
AID - 10.1038/s41467-021-26206-x [doi]
PST - epublish
SO  - Nat Commun. 2021 Oct 8;12(1):5916. doi: 10.1038/s41467-021-26206-x.