Microglia Modulate Wiring of the Embryonic Forebrain

Dysfunction of microglia, the tissue macrophages ofthe brain, has been associated with the etiology ofseveral 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 theforebrain and the laminar positioning of subsets ofneocortical 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.