TY - JOUR
T1 - CSF-1 controls cerebellar microglia and is required for motor function and social interaction
AU - Kana, Veronika
AU - Desland, Fiona A.
AU - Casanova-Acebes, Maria
AU - Ayata, Pinar
AU - Badimon, Ana
AU - Nabel, Elisa
AU - Yamamuro, Kazuhiko
AU - Sneeboer, Marjolein
AU - Tan, I. Li
AU - Flanigan, Meghan E.
AU - Rose, Samuel A.
AU - Chang, Christie
AU - Leader, Andrew
AU - Le Bourhis, Hortense
AU - Weet, Eric S.
AU - Tung, Navpreet
AU - Wroblewska, Aleksandra
AU - Lavin, Yonit
AU - See, Peter
AU - Baccarini, Alessia
AU - Ginhoux, Florent
AU - Chitu, Violeta
AU - Stanley, E. Richard
AU - Russo, Scott J.
AU - Yue, Zhenyu
AU - Brown, Brian D.
AU - Joyner, Alexandra L.
AU - De Witte, Lotje D.
AU - Morishita, Hirofumi
AU - Schaefer, Anne
AU - Merad, Miriam
N1 - Funding Information:
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. Schae-fer), 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). The authors declare no competing financial interests.
Publisher Copyright:
© 2019 Kana et al.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20182037
DO - 10.1084/jem.20182037
M3 - Article
C2 - 31350310
AN - SCOPUS:85072983559
SN - 0022-1007
VL - 216
SP - 2265
EP - 2281
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 10
ER -