Drivers and shapers of macrophages specification in the developing brain

The brain harbors two major macrophage populations: microglia reside within the brain parenchyma, while border-associated macrophages (BAMs) are situated at central nervous system (CNS) interfaces. BAMs can be further classified into distinct subsets based on their localization: perivascular macrophages surround blood vessels, meningeal macrophages reside in the leptomeninges, dura macrophages in the dura mater, and choroid plexus macrophages are confined to the choroid plexus. The environmental factors and molecular mechanisms driving the specification of these macrophage populations are still being elucidated. Deciphering the communication pathways between CNS macrophages and their tissue niches during development, homeostasis, and pathologic conditions offers significant potential for treating a wide range of brain disorders, from neurodevelopmental and neuroinflammatory diseases to neurovascular and neurodegenerative conditions. With this short review, we will address the current understanding and knowledge gaps in the field, as well as the future directions for the upcoming years.