A novel microglial subset plays a key role in myelinogenesis in developing brain

Agnieszka Wlodarczyk, Inge R. Holtman, Martin Krueger, Nir Yogev, Julia Bruttger, Reza Khorooshi, Anouk Benmamar-Badel, Jelkje J. de Boer-Bergsma, Nellie A. Martin, Khalad Karram, Isabella Kramer, Erik W. G. M. Boddeke, Ari Waisman, Bart J. L. Eggen, Trevor Owens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Microglia are resident macrophages of the central nervous system that contribute to homeostasis and neuroinflammation. Although known to play an important role in brain development, their exact function has not been fully described. Here, we show that in contrast to healthy adult and inflammation-activated cells, neonatal microglia show a unique myelinogenic and neurogenic phenotype. A CD11c(+) microglial subset that predominates in primary myelinating areas of the developing brain expresses genes for neuronal and glial survival, migration, and differentiation. These cells are the major source of insulin-like growth factor 1, and its selective depletion from CD11c(+) microglia leads to impairment of primary myelination. CD11c-targeted toxin regimens induced a selective transcriptional response in neonates, distinct from adult microglia. CD11c(+) microglia are also found in clusters of repopulating microglia after experimental ablation and in neuroinflammation in adult mice, but despite some similarities, they do not recapitulate neonatal microglial characteristics. We therefore identify a unique phenotype of neonatal microglia that deliver signals necessary for myelination and neurogenesis.

Original languageEnglish
Pages (from-to)3292-3308
Number of pages17
JournalThe EMBO Journal
Volume36
Issue number22
DOIs
Publication statusPublished - 15-Nov-2017

Keywords

  • CD11c
  • IGF1
  • microglia
  • myelinogenesis
  • CENTRAL-NERVOUS-SYSTEM
  • EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
  • POSTNATAL-DEVELOPMENT
  • ACTIVATED MICROGLIA
  • ALZHEIMERS-DISEASE
  • DEPENDENT MANNER
  • ADULT BRAIN
  • GROWTH
  • GALECTIN-1
  • CNS

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