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

Developmental & Molecular Biology

Research output: Contribution to journal › Article › peer-review

120 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 language	English (US)
Pages (from-to)	2265-2281
Number of pages	17
Journal	Journal of Experimental Medicine
Volume	216
Issue number	10
DOIs	https://doi.org/10.1084/jem.20182037
State	Published - 2019

ASJC Scopus subject areas

General Medicine

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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

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, no. 10, pp. 2265-2281. https://doi.org/10.1084/jem.20182037

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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",

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doi = "10.1084/jem.20182037",

language = "English (US)",

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pages = "2265--2281",

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AU - Desland, Fiona A.

AU - Casanova-Acebes, Maria

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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

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

Abstract

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