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88 reviewsSUMMARYThe nervous system regulates peripheral immune responses under physiological and pathological conditions, but the brain’s impact on immune system development remains unknown. Meningeal mural lymphaticendothelial cells (muLECs), embedded in the leptomeninges, form an immune niche surrounding the brainthat contributes to brain immunosurveillance. Here, we report that the brain controls the development of muLECs via a specialized glial subpopulation, slc6a11b+ radial astrocytes (RAs), a process modulated by neuralactivity in zebrafish. slc6a11b+ RAs, with processes extending to the meninges, govern muLEC formation byexpressing vascular endothelial growth factor C (vegfc). Moreover, neural activity regulates muLEC development, and this regulation requires Vegfc in slc6a11b+ RAs. Intriguingly, slc6a11b+ RAs cooperate with calcium-binding EGF domain 1 (ccbe1)+ fibroblasts to restrict muLEC growth on the brain surface via controllingmature Vegfc distribution. Thus, our study uncovers a glia-mediated and neural-activity-regulated control ofbrain lymphatic development and highlights the importance of inter-tissue cellular cooperation indevelopment.
