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

CSF-1 controls cerebellar microglia and is required for motor function and social interaction
Title:
CSF-1 controls cerebellar microglia and is required for motor function and social interaction
Other Titles:
Journal of Experimental Medicine
Keywords:
Publication Date:
26 July 2019
Citation:
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. Sweet, Navpreet Tung, Aleksandra Wroblewska, Yonit Lavin, Peter See, Alessia Baccarini, Florent 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; CSF-1 controls cerebellar microglia and is required for motor function and social interaction. J Exp Med 7 October 2019; 216 (10): 2265–2281. doi: https://doi.org/10.1084/jem.20182037
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.
License type:
http://creativecommons.org/licenses/by-nc-sa/4.0/
Funding Info:
This work was supported by National Institutes of Health grants R01CA154947, R01MH104559, and U19AI128949 (M. Merad), an Advanced Postdoc Mobility Fellowship of the Swiss National Foundation (V. Kana), a postdoctoral fellowship from the Human Frontier Science Program Organization (LT000110/ 2015-L/1; M. Casanova-Acebes), a National Institutes of Health Director New Innovator Award (DP2 MH100012-01; A. Schaefer), National Institutes of Health grant 1RF1 AG054011-01 (A.Schaefer), a Brain and Behavior Research Foundation NARSAD Young Investigator Award (25065; P. Ayata), National Institutes of Health grant T32 AG049688 (A. Baccarini), National Institute of Mental Health grant F30MH111143 (E. Nabel), National Institutes of Health grant R21MH106919 (H. Morishita), National Eye Institute grants R01EY024918, R01EY 026053, and R21EY026702 (H. Morishita), National Institute of Neurological Disorders and Stroke grant R21NS105119 (H. Morishita), the Naito Foundation (K. Yamamuro), the Uehara Memorial Foundation (K. Yamamuro), the Seaver Foundation (E. Nabel), an EMBO Young Investigator Programme award (F. Ginhoux), National Research Foundation Senior Investigatorship grant NFR2016NRF-NRFI001-02 (F. Ginhoux), the Singapore Immunology Network Core Funding (F. Ginhoux and P. See), and National Institutes of Health grant R01 NS091519 (E.R. Stanley).
Description:
ISSN:
0022-1007
1540-9538
Files uploaded: