title: Microglia modulate wiring of the embryonic forebrain.
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.
authors.affiliation: 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.
authors.forename: Paola
authors.initials: P
authors.lastname: Squarzoni
authors.affiliation: 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.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Oller
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building Nos. 3-4, BIOPOLIS 138648, Singapore.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Hoeffel
authors.affiliation: École Normale Supérieure, Institut de Biologie de l'ENS, IBENS, INSERM, U1024, CNRS, UMR 8197, 46 rue d'Ulm, 75230 Paris Cedex 05, France.
authors.forename: Lorena
authors.initials: L
authors.lastname: Pont-Lezica
authors.affiliation: École Normale Supérieure, Institut de Biologie de l'ENS, IBENS, INSERM, U1024, CNRS, UMR 8197, 46 rue d'Ulm, 75230 Paris Cedex 05, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rostaing
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building Nos. 3-4, BIOPOLIS 138648, Singapore.
authors.forename: Donovan
authors.initials: D
authors.lastname: Low
authors.affiliation: École Normale Supérieure, Institut de Biologie de l'ENS, IBENS, INSERM, U1024, CNRS, UMR 8197, 46 rue d'Ulm, 75230 Paris Cedex 05, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Bessis
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, IMMUNOS Building Nos. 3-4, BIOPOLIS 138648, Singapore.
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.affiliation: 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.
authors.forename: Sonia
authors.initials: S
authors.lastname: Garel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D055495:Neurogenesis; D016548:Prosencephalon / Q000166:cytology* / Q000196:embryology / Q000502:physiology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D023062:Receptors, Interleukin-8A; C484963:Tyrobp protein, mouse; D016186:Receptor, Macrophage Colony-Stimulating Factor