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Updated: Jan 11, 2026
Author Spotlight: In Vitro Co-Culture Model for Studying Microglia-Neuronal Interactions in Disease Conditions
Published on: July 26, 2024
Microglial colonization of the developing mouse brain is controlled by both microglial and neural CSF-1
Cécile Bridlance1,2,3, Sarah Viguier1,2,3, Nicolas Olivié1,2,3
1Centre Interdisciplinaire de Recherche en Biologie (CIRB), Collège de France, Université PSL, CNRS, INSERM, 75005, Paris, France.
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.
Insights
Brain microglia colonization and proliferation depend on colony-stimulating factor 1 (CSF-1). Neural and intrinsic CSF-1 sources guide microglial distribution and expansion during development, impacting brain health and disease.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Microglia, brain-resident macrophages, are vital for brain development and function.
- The mechanisms governing microglial colonization and proliferation in the developing brain are not fully understood.
Purpose of the Study:
- To investigate the mechanisms controlling microglial colonization and proliferation in the developing mouse forebrain.
- To identify the role of colony-stimulating factor 1 (CSF-1) in microglial development.
Main Methods:
- Conditional inactivation of the colony-stimulating factor 1 (Csf1) gene in mice.
- Analysis of microglial distribution and proliferation patterns in the developing brain.
- Investigation of CSF-1 sources, including neural and intrinsic microglial sources.
Main Results:
- Two distinct waves of microglial proliferation were observed in the developing mouse forebrain.
- Microglial colonization and proliferation are independent of neuronal activity.
- Neural CSF-1, primarily from cortical progenitors and neurons, is crucial for embryonic cortical microglial distribution and proliferation.
- Intrinsic CSF-1 from axon tract-associated microglia (ATM)-like cells supports their sustained proliferation.
Conclusions:
- Microglial development relies on distinct, local, and cell-type-specific sources of CSF-1.
- Understanding these CSF-1-dependent mechanisms is critical for comprehending microglial colonization in both health and disease.
