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

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

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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
JournalE M B O Journal
Volume36
Issue number22
Pages (from-to)3292-3308
ISSN0261-4189
DOIs
Publication statusPublished - 2017

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Wlodarczyk, A., Holtman, I., Krueger, M., Yogev, N., Bruttger, J., Khorooshi, R. M. H., Benmamar-Badel, A., de Boer Bergsma, J., Martin, N. A., Karram, K., Kramer, I., Boddeke, E. W. G. M., Waisman, A., Eggen, B. J. L., & Owens, T. (2017). A novel microglial subset plays a key role in myelinogenesis in developing brain. E M B O Journal, 36(22), 3292-3308. https://doi.org/10.15252/embj.201696056