Microglia modulate wiring of the embryonic forebrain.

By P. Squarzoni, Guillaume Oller, G. Hoeffel, Lorena Pont‐Lezica, P. Rostaing, Donovan Low, A. Bessis, Florent Ginhoux, S. Garel. Cell Reports, 2014

594 citations recorded by the source corpus.

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.

Subfields: Developmental Neuroscience, Immunology, Neurology

View Paper: https://www.semanticscholar.org/paper/0020259518d6e1e3cee28658f9a49e0fd2ae78a9

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In Developmental Neuroscience

  1. Robin J. M. Franklin
  2. Beth Stevens
  3. Amanda Sierra
  4. C. Iadecola

In Immunology

  1. Beth Stevens
  2. V. Perry
  3. Florent Ginhoux
  4. M. Cragg

In Neurology

  1. Beth Stevens
  2. V. Perry
  3. Robin J. M. Franklin
  4. Florent Ginhoux
  5. Amanda Sierra
  6. C. Iadecola
  7. R. Ransohoff
  8. C. Cunningham

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