Mast Cells in the Developing Brain

Brain development requires the coordination of numerous cell types including neurons, glia, and immune cells. Mast cells (MCs) are tissue-resident innate immune cells canonically known for their role in allergic responses and anaphylaxis. In the central nervous system (CNS), MCs populate the meninges and brain parenchyma, exhibiting dynamic, age- and region-dependent changes during neurodevelopment. Emerging evidence indicates that CNS-resident MCs may influence key neurodevelopmental processes through bidirectional cross talk with microglia, regulation of blood-brain barrier permeability, and orchestration of peripheral immune cell recruitment to the developing brain. However, significant challenges exist regarding tools to precisely dissect the contribution of MCs in these processes. Clinically, MC-derived mediators including interleukin 6 and histamine have been implicated in neurodevelopmental disorder (NDD) etiology, with epidemiological links between allergic disease and elevated risk for NDD. This review synthesizes current knowledge of MC biology in the developing brain and highlights critical gaps requiring further investigation to understand their role in neurodevelopment and neurological disease susceptibility.