The meninges are a protective and nutritious tissue that surrounds the central nervous system (CNS) and supports the brain. Recent data, including from our team, have revealed that the meninges contain a myriad of immune cells, such as meningeal macrophages (MM). Interestingly, the meninges penetrate the brain parenchyma and contact sub-structures such as the hippocampus, which is one of the main neurogenic niches. This strategic position of the meninges and thus MM raised the hypothesis that these cells could play a role in hippocampal neonatal neurogenesis. To address this question, we used novel chemical and genetic models to deplete MM in neonatal mice and measured the impact of this depletion on neurogenesis. Preliminary data show that early MM depletion decreased neurogenesis in the hippocampus of neonates with a long-term effect on neuronal progenitors’ number, and subsequent memory impairments in adult mice. Multi-RNA sequencing analyses of meningeal and hippocampal tissues associated with computed cell-cell communication algorithms enabled us to identify a panel of ligands that could support communication between MM and neural stem cells of the hippocampus. Using in vivo and in vitro models, we identified MM-derived candidate ligands whose blockade decreases proliferation of neuronal progenitors. This work could ultimately uncover the involvement of MM in brain development, thereby paving the way for a potential role of these cells in physiological and pathological condition (i.e., onset of neurodevelopmental disorders.)