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

EMBO J. 2017 Nov 15;36(22):3292-3308. doi: 10.15252/embj.201696056. Epub 2017 Sep 28.

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.

Keywords: CD11c; IGF1; microglia; myelinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Animals
  • Animals, Newborn
  • Biomarkers / metabolism
  • Brain / cytology*
  • Brain / embryology*
  • Brain / ultrastructure
  • CD11c Antigen / metabolism
  • Cell Aggregation
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Insulin-Like Growth Factor I / metabolism
  • Mice, Inbred C57BL
  • Microglia / metabolism*
  • Myelin Sheath / metabolism*
  • Neural Plate / metabolism
  • Neurogenesis*
  • Up-Regulation / genetics

Substances

  • Biomarkers
  • CD11c Antigen
  • Insulin-Like Growth Factor I