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 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

doi:10.1084/jem.20182037

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

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

124 Citations (Scopus)

Résumé

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.

langue originale	Anglais
Pages (de - à)	2265-2281
Nombre de pages	17
journal	Journal of Experimental Medicine
Volume	216
Numéro de publication	10
Les DOIs	https://doi.org/10.1084/jem.20182037
état	Publié - 1 janv. 2019
Modification externe	Oui

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10.1084/jem.20182037

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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

@article{779e88795b15477f823a61c817219342,

title = "CSF-1 controls cerebellar microglia and is required for motor function and social interaction",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2019 Kana et al.",

year = "2019",

month = jan,

day = "1",

doi = "10.1084/jem.20182037",

language = "English",

volume = "216",

pages = "2265--2281",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

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Kana, V, Desland, FA, Casanova-Acebes, M, Ayata, P, Badimon, A, Nabel, E, Yamamuro, K, Sneeboer, M, Tan, IL, Flanigan, ME, Rose, SA, Chang, C, Leader, A, Le Bourhis, H, Weet, ES, Tung, N, Wroblewska, A, Lavin, Y, See, P, Baccarini, A, Ginhoux, F, Chitu, V, Stanley, ER, Russo, SJ, Yue, Z, Brown, BD, Joyner, AL, De Witte, LD, Morishita, H, Schaefer, A & Merad, M 2019, 'CSF-1 controls cerebellar microglia and is required for motor function and social interaction', Journal of Experimental Medicine, VOL. 216, Numéro 10, p. 2265-2281. https://doi.org/10.1084/jem.20182037

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

PY - 2019/1/1

Y1 - 2019/1/1

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 -