Macrophage-mediated refinement of the dural lymphatic regulates social behavior

The meningeal lymphatic vasculature has recently emerged as a central player in the regulation of brain function under normal and pathological conditions. The dorsal meningeal/dural lymphatics expand uniquely postnatally during a critical window for brain maturation. The mechanisms driving their development and function, however, remain poorly understood. Here, we demonstrate that the developing dorsal meningeal lymphatic vasculature, contrary to peripheral counterparts, undergoes defined refinement orchestrated by cell death and phagocytosis by meningeal macrophages. Alteration of this refinement is observed in the BTBR mouse model of autism spectrum disorder (ASD) and appears to regulate ASD-like social behavior. Together, our results demonstrate a new pathway regulating meningeal lymphatic development that may contribute to brain maturation and function.