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.小胶质细胞（Microglia）是脑固有巨噬细胞，对大脑发育、功能及稳态维持至关重要。在胚胎发育过程中，卵黄囊来源的小胶质细胞祖细胞会按照明确的时空模式定植并充盈大脑。然而，驱动小胶质细胞定植与增殖的分子机制目前尚不清楚。本研究通过对集落刺激因子1（Colony Stimulating Factor 1，Csf1）条件性失活模型开展单细胞RNA测序（scRNA-seq）分析，揭示出胚胎皮层小胶质细胞关键依赖神经源性Csf1：该因子主要由皮层祖细胞产生，亦可由有丝分裂后神经元合成；且Csf1的作用具有局部性、剂量依赖性与瞬时性。此外，由ATM表达的内源性Csf1可促进其在发育热点区域的持续增殖。