Format

Send to

Choose Destination
J Exp Med. 2019 Jul 26. pii: jem.20182037. doi: 10.1084/jem.20182037. [Epub ahead of print]

CSF-1 controls cerebellar microglia and is required for motor function and social interaction.

Author information

1
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
2
Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
3
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
4
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
5
Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY.
6
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY.
7
Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY.
8
Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
9
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
10
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
11
Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY.
12
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
13
Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.
14
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY.
15
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY miriam.merad@mssm.edu.
#
Contributed equally

Abstract

Microglia, the brain resident macrophages, critically shape forebrain neuronal circuits. However, their precise function in the cerebellum is unknown. Here we show that human and mouse cerebellar microglia express a unique molecular program distinct from forebrain microglia. Cerebellar microglial identity was driven by the CSF-1R ligand CSF-1, independently of the alternate CSF-1R ligand, IL-34. Accordingly, CSF-1 depletion from Nestin+ cells led to severe depletion and transcriptional alterations of cerebellar microglia, while microglia in the forebrain remained intact. Strikingly, CSF-1 deficiency and alteration of cerebellar microglia were associated with reduced Purkinje cells, altered neuronal function, and defects in motor learning and social novelty interactions. These findings reveal a novel CSF-1-CSF-1R signaling-mediated mechanism that contributes to motor function and social behavior.

PMID:
31350310
DOI:
10.1084/jem.20182037

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center