PUBLICATION
Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges
- Authors
- Shibata-Germanos, S., Goodman, J.R., Grieg, A., Trivedi, C.A., Benson, B.C., Foti, S.C., Faro, A., Castellan, R.F.P., Correra, R.M., Barber, M., Ruhrberg, C., Weller, R.O., Lashley, T., Iliff, J.J., Hawkins, T.A., Rihel, J.
- ID
- ZDB-PUB-191108-27
- Date
- 2019
- Source
- Acta Neuropathologica 139(2): 383-401 (Journal)
- Registered Authors
- Faro, Ana, Rihel, Jason, Trivedi, Chintan
- Keywords
- CNS lymphatics, CNS macrophages, Lymphatics, Macrophages, Meningeal lymphatics
- MeSH Terms
-
- Adult
- Aged
- Aged, 80 and over
- Amyloid beta-Peptides
- Animals
- Brain/pathology*
- Endothelial Cells/pathology*
- Endothelial Cells/physiology*
- Female
- Humans
- Lymphatic System/pathology*
- Male
- Meninges/pathology*
- Mice
- Zebrafish
- PubMed
- 31696318 Full text @ Acta Neuropathol.
Citation
Shibata-Germanos, S., Goodman, J.R., Grieg, A., Trivedi, C.A., Benson, B.C., Foti, S.C., Faro, A., Castellan, R.F.P., Correra, R.M., Barber, M., Ruhrberg, C., Weller, R.O., Lashley, T., Iliff, J.J., Hawkins, T.A., Rihel, J. (2019) Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges. Acta Neuropathologica. 139(2):383-401.
Abstract
The vertebrate CNS is surrounded by the meninges, a protective barrier comprised of the outer dura mater and the inner leptomeninges, which includes the arachnoid and pial layers. While the dura mater contains lymphatic vessels, no conventional lymphatics have been found within the brain or leptomeninges. However, non-lumenized cells called Brain/Mural Lymphatic Endothelial Cells or Fluorescent Granule Perithelial cells (muLECs/BLECs/FGPs) that share a developmental program and gene expression with peripheral lymphatic vessels have been described in the meninges of zebrafish. Here we identify a structurally and functionally similar cell type in the mammalian leptomeninges that we name Leptomeningeal Lymphatic Endothelial Cells (LLEC). As in zebrafish, LLECs express multiple lymphatic markers, containing very large, spherical inclusions, and develop independently from the meningeal macrophage lineage. Mouse LLECs also internalize macromolecules from the cerebrospinal fluid, including Amyloid-β, the toxic driver of Alzheimer's disease progression. Finally, we identify morphologically similar cells co-expressing LLEC markers in human post-mortem leptomeninges. Given that LLECs share molecular, morphological, and functional characteristics with both lymphatics and macrophages, we propose they represent a novel, evolutionary conserved cell type with potential roles in homeostasis and immune organization of the meninges.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping