RRC ID 89757
Author Li J, Liu MJ, Du WJ, Peng XL, Deng H, Zi HX, Shang HB, Du JL.
Title Neural-activity-regulated and glia-mediated control of brain lymphatic development.
Journal Cell
Abstract The nervous system regulates peripheral immune responses under physiological and pathological conditions, but the brain's impact on immune system development remains unknown. Meningeal mural lymphatic endothelial cells (muLECs), embedded in the leptomeninges, form an immune niche surrounding the brain that 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 neural activity in zebrafish. slc6a11b+ RAs, with processes extending to the meninges, govern muLEC formation by expressing 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 controlling mature Vegfc distribution. Thus, our study uncovers a glia-mediated and neural-activity-regulated control of brain lymphatic development and highlights the importance of inter-tissue cellular cooperation in development.
Volume 188(12)
Pages 3274-3290.e16
Published 2025-6-12
DOI 10.1016/j.cell.2025.04.008
PII S0092-8674(25)00410-6
PMID 40311620
MeSH Animals Astrocytes / metabolism Brain* / cytology Brain* / embryology Brain* / metabolism Endothelial Cells / cytology Endothelial Cells / metabolism Lymphangiogenesis* Lymphatic Vessels Meninges / cytology Meninges / metabolism Neuroglia* / metabolism Neurons / metabolism Vascular Endothelial Growth Factor C / metabolism Zebrafish / metabolism Zebrafish Proteins / metabolism
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Zebrafish UAS:GFP, UAS:GCaMP6s