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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Squarzoni P,Oller G,Hoeffel G,Pont-Lezica L,Rostaing P,Low D,Bessis A,Ginhoux F,Garel Sdoi
10.1016/j.celrep.2014.07.042subject
Has Abstractpub_date
2014-09-11 00:00:00pages
1271-9issue
5issn
2211-1247pii
S2211-1247(14)00626-3journal_volume
8pub_type
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