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Nat Commun. 2014 Nov 26;5:5611. doi: 10.1038/ncomms6611.

Neural progenitor cells orchestrate microglia migration and positioning into the developing cortex.

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Neuroimmunology Unit, Division of Neuroscience, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, 20132 Milan, Italy.
Department of Biosciences, University of Milan, 20100 Milan, Italy.
Institute of Experimental Immunology, University of Zurich, CH-8057 Zürich, Switzerland.
Dipartimento di Biotecnologie e Bioscienze, University Milano-Bicocca, 20100 Milan, Italy.
Department of Neurology, Institute of Experimental Neurology (INSPE), Vita Salute San Raffaele University, 20132 Milan, Italy.


Microglia are observed in the early developing forebrain and contribute to the regulation of neurogenesis through still unravelled mechanisms. In the developing cerebral cortex, microglia cluster in the ventricular/subventricular zone (VZ/SVZ), a region containing Cxcl12-expressing basal progenitors (BPs). Here we show that the ablation of BP as well as genetic loss of Cxcl12 affect microglia recruitment into the SVZ. Ectopic Cxcl12 expression or pharmacological blockage of CxcR4 further supports that Cxcl12/CxcR4 signalling is involved in microglial recruitment during cortical development. Furthermore, we found that cell death in the developing forebrain triggers microglial proliferation and that this is mediated by the release of macrophage migration inhibitory factor (MIF). Finally, we show that the depletion of microglia in mice lacking receptor for colony-stimulating factor-1 (Csf-1R) reduces BPs into the cerebral cortex.

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