Microglial colonization is shaped by intrinsic and extrinsic CSF-1 during early forebrain development

Microglia are brain-resident macrophages critical for cerebral development, function and homeostasis. During development, yolk-sac-derived microglial progenitors colonize and populate the brain following a well-defined spatiotemporal pattern. However, the mechanisms driving microglial colonization and proliferation are largely unknown. Herein, using scRNA-seq of conditional inactivation of Colony Stimulating Factor 1 (Csf1), we revealed that embryonic cortical microglia critically rely on neural Csf1, mainly produced by cortical progenitors but also by post-mitotic neurons, and that the action of Csf1 is local, dose-dependent and transient. Alongside, intrinsic Csf1 expressed by ATM contributed to their sustained proliferation at developmental hotspots.