2025-04-30 中国科学院(CAS)
<関連情報>
- https://english.cas.cn/newsroom/research_news/life/202505/t20250506_1042516.shtml
- https://www.cell.com/cell/abstract/S0092-8674(25)00410-6
脳リンパ管発達の神経活性制御とグリア介在制御 Neural-activity-regulated and glia-mediated control of brain lymphatic development
Jia Li (李佳) ∙ Ming-Jian Liu (刘明剑) ∙ Wen-Jie Du (杜文杰) ∙ … ∙ Hua-Xing Zi (訾化星) ∙ Han-Bing Shang (尚寒冰) ∙ Jiu-Lin Du (杜久林)
Cell Published:April 30, 2025
DOI:https://doi.org/10.1016/j.cell.2025.04.008
Graphical abstract
Highlights
- slc6a11b+ radial astrocytes (RAs) are the primary source of Vegfc in the brain
- Vegfc produced by slc6a11b+ RAs controls muLEC development
- Neural activity modulates muLEC development via Vegfc expressed in slc6a11b+ RAs
- slc6a11b+ RAs work with ccbe1+ fibroblasts to restrict muLEC growth on brain surface
Summary
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.
