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

Benedetta Arnò, Francesca Grassivaro, Chiara Rossi, Andrea Bergamaschi, Valentina Castiglioni, Roberto Furlan, Melanie Greter, Rebecca Favaro, Giancarlo Comi, Burkhard Becher, Gianvito Martino and Luca Muzio ()
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Benedetta Arnò: Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute
Francesca Grassivaro: Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute
Chiara Rossi: Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute
Andrea Bergamaschi: Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute
Valentina Castiglioni: University of Milan
Roberto Furlan: Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute
Melanie Greter: Institute of Experimental Immunology, University of Zurich
Rebecca Favaro: University Milano-Bicocca
Giancarlo Comi: Institute of Experimental Neurology (INSPE), Vita Salute San Raffaele University
Burkhard Becher: Institute of Experimental Immunology, University of Zurich
Gianvito Martino: Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute
Luca Muzio: Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract 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.

Date: 2014
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DOI: 10.1038/ncomms6611

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