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

Veronika Kana, Fiona A. Desland, Maria Casanova-Acebes, Pinar Ayata, Ana Badimon, Elisa Nabel, Kazuhiko Yamamuro, Marjolein Sneeboer, I. Li Tan, Meghan E. Flanigan, Samuel A. Rose, Christie Chang, Andrew Leader, Hortense Le Bourhis, Eric S. Weet, Navpreet Tung, Aleksandra Wroblewska, Yonit Lavin, Peter See, Alessia BaccariniFlorent Ginhoux, Violeta Chitu, E. Richard Stanley, Scott J. Russo, Zhenyu Yue, Brian D. Brown, Alexandra L. Joyner, Lotje D. De Witte, Hirofumi Morishita, Anne Schaefer, Miriam Merad

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2265-2281
Number of pages17
JournalJournal of Experimental Medicine
Volume216
Issue number10
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kana, V., Desland, F. A., Casanova-Acebes, M., Ayata, P., Badimon, A., Nabel, E., Yamamuro, K., Sneeboer, M., Tan, I. L., Flanigan, M. E., Rose, S. A., Chang, C., Leader, A., Le Bourhis, H., Weet, E. S., Tung, N., Wroblewska, A., Lavin, Y., See, P., ... Merad, M. (2019). CSF-1 controls cerebellar microglia and is required for motor function and social interaction. Journal of Experimental Medicine, 216(10), 2265-2281. https://doi.org/10.1084/jem.20182037