1. CSF-1 controls cerebellar microglia and is required for motor function and social interaction
- Author
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Violeta Chitu, Samuel A. Rose, Anne Schaefer, Aleksandra Wroblewska, Brian D. Brown, Ana Badimon, Lotje de Witte, Zhenyu Yue, Kazuhiko Yamamuro, Maria Casanova-Acebes, Andrew Leader, Pinar Ayata, Alessia Baccarini, Florent Ginhoux, I-li Tan, Yonit Lavin, Hortense Le Bourhis, Scott J. Russo, Veronika Kana, Christie Chang, Alexandra L. Joyner, Eric S. Sweet, Peter See, Hirofumi Morishita, Navpreet Tung, Miriam Merad, Elisa M. Nabel, E. Richard Stanley, Fiona Desland, Meghan E. Flanigan, and Marjolein A. M. Sneeboer
- Subjects
0301 basic medicine ,Macrophage Colony-Stimulating Factor ,Immunology ,Science program ,Library science ,Receptor, Macrophage Colony-Stimulating Factor ,Motor function ,Article ,03 medical and health sciences ,Mice ,030104 developmental biology ,0302 clinical medicine ,Innovator ,Political science ,Immunology and Allergy ,Animals ,Interpersonal Relations ,Microglia ,10. No inequality ,030217 neurology & neurosurgery ,Research Articles ,Signal Transduction - Abstract
Microglia are a heterogeneous population whose identity and function are dictated by signals from their microenvironment. Kana et al. show CSF-1 signaling is critical for cerebellar microglial transcriptional identity and homeostasis, and that altering the CSF-1–CSF-1R axis leads to motor and behavioral defects., 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.
- Published
- 2019