PUBLICATION
Neural-activity-regulated and glia-mediated control of brain lymphatic development
- Authors
- Li, J., Liu, M.J., Du, W.J., Peng, X.L., Deng, H., Zi, H.X., Shang, H.B., Du, J.L.
- ID
- ZDB-PUB-250502-3
- Date
- 2025
- Source
- Cell : (Journal)
- Registered Authors
- Keywords
- VEGFC, development, fibroblast, immune system, leptomeninges, meningeal mural lymphatic endothelial cells, nervous system, neural activity, radial astrocyte
- MeSH Terms
- none
- PubMed
- 40311620 Full text @ Cell
Citation
Li, J., Liu, M.J., Du, W.J., Peng, X.L., Deng, H., Zi, H.X., Shang, H.B., Du, J.L. (2025) Neural-activity-regulated and glia-mediated control of brain lymphatic development. Cell. :. Epub ahead of print.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping