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

• Agnieszka Wlodarczyk ^[1] ; Inge R Holtman ^[5] ; Martin Krueger ^[2] ; Nir Yogev ^[6] ; Julia Bruttger ^[7] ; Reza Khorooshi ^[1] ; Anouk Benmamar‐Badel ^[3] ; Jelkje J de Boer‐Bergsma ^[8] ; Nellie A Martin ^[4] ; Khalad Karram ^[7] ; Isabella Kramer ^[1] ; Erik WGM Boddeke ^[5] ; Ari Waisman ^[7] ; Bart JL Eggen ^[5] ; Trevor Owens ^[1]
  1. [1] University of Southern Denmark

     University of Southern Denmark

     Dinamarca

     
  2. [2] University of Leipzig

     University of Leipzig

     Kreisfreie Stadt Leipzig, Alemania

     
  3. [3] Institute for Molecular Medicine

     Institute for Molecular Medicine

     Estados Unidos

     
  4. [4] Odense University Hospital

     Odense University Hospital

     Dinamarca

     
  5. [5] 2 Department of Neuroscience, Medical Physiology University Medical Center Groningen University of Groningen Groningen The Netherlands
  6. [6] 4 Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg University of Mainz Mainz Germany; 8Present address: Department of Neurology University Medical Center of the Johannes Gutenberg University of Mainz Mainz Germany
  7. [7] 4 Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg University of Mainz Mainz Germany
  8. [8] 6 Department of Genetics University Medical Center Groningen University of Groningen Groningen The Netherlands

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 36, Nº. 22, 2017, págs. 3292-3308
• Idioma: inglés
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• Resumen

  • 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.