Microglial colonization of the developing mouse brain is controlled by both microglial and neural CSF-1

Microglia are brain-resident macrophages critical for cerebral development, function, and homeostasis. During development, yolk sac-derived microglial progenitor cells colonize and populate the brain following a well-defined spatiotemporal pattern. However, the mechanisms controlling microglial colonization and proliferation remain largely unknown. Here, we describe two broad waves of microglial proliferation in the developing mouse forebrain. Microglia accumulate in transient hotspots, in a proliferative axon tract-associated microglia (ATM)-like state. Prenatal and early postnatal patterns of microglial colonization do not rely on neuronal activity. Instead, using conditional inactivation of the microglial regulator colony-stimulating factor 1 (Csf1) gene, we reveal that the distribution and proliferation of embryonic cortical microglia critically rely on neural CSF-1, mainly produced by cortical progenitor cells but also by post-mitotic neurons, with the action of CSF-1 being local, dose-dependent, and transient. In addition, intrinsic CSF-1 expressed by ATM microglia contributes to their sustained proliferation in developmental hotspots. Our study reveals that microglia rely on distinct, local, and cell-type-specific sources of CSF-1 for their developmental distribution, which has major implications for understanding how microglia colonize the brain in health and disease.

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Publication Details

Journal
The EMBO Journal
Published
2025-11-17
DOI
https://doi.org/10.1038/s44318-025-00625-8
Primary Topic
Neuroinflammation and Neurodegeneration Mechanisms
Type
article
Field-Weighted Citation Impact
0.00
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article

Microglial colonization of the developing mouse brain is controlled by both microglial and neural CSF-1

Melanie Greter, Morgane Sonia Thion, Guillermina López‐Bendito, Florent Ginhoux et al.
The EMBO Journal
Neuroinflammation and Neurodegeneration Mechanisms
article

Microglial colonization of the developing mouse brain is controlled by both microglial and neural CSF-1

Melanie Greter, Morgane Sonia Thion, Guillermina López‐Bendito, Florent Ginhoux, Jean X. Jiang, Burkhard Becher, Sonia Garel, Edmond Dupont, Benjamin Mathieu, Cécile Bridlance, Aymeric Silvin, Sarah Viguier, Nicolas Olivié, Ety Klinger, Dorine Thobois
article en

Abstract

Microglia are brain-resident macrophages critical for cerebral development, function, and homeostasis. During development, yolk sac-derived microglial progenitor cells colonize and populate the brain following a well-defined spatiotemporal pattern. However, the mechanisms controlling microglial colonization and proliferation remain largely unknown. Here, we describe two broad waves of microglial proliferation in the developing mouse forebrain. Microglia accumulate in transient hotspots, in a proliferative axon tract-associated microglia (ATM)-like state. Prenatal and early postnatal patterns of microglial colonization do not rely on neuronal activity. Instead, using conditional inactivation of the microglial regulator colony-stimulating factor 1 (Csf1) gene, we reveal that the distribution and proliferation of embryonic cortical microglia critically rely on neural CSF-1, mainly produced by cortical progenitor cells but also by post-mitotic neurons, with the action of CSF-1 being local, dose-dependent, and transient. In addition, intrinsic CSF-1 expressed by ATM microglia contributes to their sustained proliferation in developmental hotspots. Our study reveals that microglia rely on distinct, local, and cell-type-specific sources of CSF-1 for their developmental distribution, which has major implications for understanding how microglia colonize the brain in health and disease.

The EMBO JournalVol. 45(1)
Centre National de la Recherche Scientifique (FR), Allen Institute for Brain Science (US), Consejo Superior de Investigaciones Científicas (ES), Inserm (FR), The University of Texas at San Antonio Health Science Center (US), Université Sorbonne Nouvelle (FR), University of Zurich (CH), Université Paris Sciences et Lettres (FR), Singapore Immunology Network (SG), Institut Gustave Roussy (FR), École Normale Supérieure - PSL (FR), Sorbonne Université (FR), Instituto de Neurociencias (ES), Centre Interdisciplinaire de Recherche en Biologie (FR), Institut de Biologie de l'École Normale Supérieure (FR), VIB-KU Leuven Center for Brain & Disease Research (BE)
Openalex Percentile: Top 58%
Neuroinflammation and Neurodegeneration Mechanisms
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