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Updated: Apr 20, 2026
Author Spotlight: Exploring Cell Migration and Gene Roles in the Developing Brain
Published on: March 8, 2024
Neural progenitor cells orchestrate microglia migration and positioning into the developing cortex
Benedetta Arnò1, Francesca Grassivaro1, Chiara Rossi1
1Neuroimmunology Unit, Division of Neuroscience, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, 20132 Milan, Italy.
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.
Insights
Microglia in the developing brain are recruited to the subventricular zone via Cxcl12 signaling. Microglial depletion reduces basal progenitor cells in the cerebral cortex.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Microglia, the brain's immune cells, are present in the early developing forebrain.
- Their precise role in regulating neurogenesis remains unclear.
- Microglia are known to cluster in the ventricular/subventricular zone (VZ/SVZ) of the developing cerebral cortex.
Purpose of the Study:
- To investigate the mechanisms of microglial recruitment into the developing cerebral cortex.
- To elucidate the role of Cxcl12/CxcR4 signaling in this process.
- To understand how cell death influences microglial activity and its impact on neural progenitor cells.
Main Methods:
- Ablation of basal progenitors (BPs) and genetic deletion of Cxcl12.
- Manipulation of Cxcl12 expression and CxcR4 blockade.
- Induction of cell death and depletion of microglia using Csf-1R knockout models.
Main Results:
- Ablation of BPs and loss of Cxcl12 impaired microglial recruitment to the SVZ.
- Cxcl12/CxcR4 signaling was confirmed to be crucial for microglial recruitment.
- Forebrain cell death stimulated microglial proliferation via macrophage migration inhibitory factor (MIF).
- Microglial depletion led to a reduction in cortical BPs.
Conclusions:
- Cxcl12 signaling is essential for microglial recruitment to the developing cortex.
- Macrophage migration inhibitory factor mediates microglial proliferation in response to cell death.
- Microglia play a critical role in regulating the number of basal progenitors during cortical development.
