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 - 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.
UR - http://www.scopus.com/inward/record.url?scp=85072983559&partnerID=8YFLogxK
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 -