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Cell Rep. 2014 Sep 11;8(5):1271-9. doi: 10.1016/j.celrep.2014.07.042. Epub 2014 Aug 21.

Microglia modulate wiring of the embryonic forebrain.

Author information

1
École Normale Supérieure, Institut de Biologie de l'ENS, IBENS, INSERM, U1024, CNRS, UMR 8197, Brain Development and Plasticity Team, 46 rue d'Ulm, 75230 Paris Cedex 05, France.
2
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building Nos. 3-4, BIOPOLIS 138648, Singapore.
3
École Normale Supérieure, Institut de Biologie de l'ENS, IBENS, INSERM, U1024, CNRS, UMR 8197, 46 rue d'Ulm, 75230 Paris Cedex 05, France.
4
École Normale Supérieure, Institut de Biologie de l'ENS, IBENS, INSERM, U1024, CNRS, UMR 8197, Brain Development and Plasticity Team, 46 rue d'Ulm, 75230 Paris Cedex 05, France. Electronic address: garel@biologie.ens.fr.

Abstract

Dysfunction of microglia, the tissue macrophages of the brain, has been associated with the etiology of several neuropsychiatric disorders. Consistently, microglia have been shown to regulate neurogenesis and synaptic maturation at perinatal and postnatal stages. However, microglia invade the brain during mid-embryogenesis and thus could play an earlier prenatal role. Here, we show that embryonic microglia, which display a transiently uneven distribution, regulate the wiring of forebrain circuits. Using multiple mouse models, including cell-depletion approaches and cx3cr1(-/-), CR3(-/-), and DAP12(-/-) mutants, we find that perturbing microglial activity affects the outgrowth of dopaminergic axons in the forebrain and the laminar positioning of subsets of neocortical interneurons. Since defects in both dopamine innervation and cortical networks have been linked to neuropsychiatric diseases, our study provides insights into how microglial dysfunction can impact forebrain connectivity and reveals roles for immune cells during normal assembly of brain circuits.

PMID:
25159150
DOI:
10.1016/j.celrep.2014.07.042
[Indexed for MEDLINE]
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