Mural lymphatic endothelial cells regulate meningeal angiogenesis in the zebrafish
- Bower, N.I., Koltowska, K., Pichol-Thievend, C., Virshup, I., Paterson, S., Lagendijk, A.K., Wang, W., Lindsey, B.W., Bent, S.J., Baek, S., Rondon-Galeano, M., Hurley, D.G., Mochizuki, N., Simons, C., Francois, M., Wells, C.A., Kaslin, J., Hogan, B.M.
- Nature Neuroscience 20(6): 774-783 (Journal)
- Registered Authors
- Hogan, Ben M., Kaslin, Jan, Mochizuki, Naoki, Paterson, Scott
- GEO:GSE97650, GEO:GSE97651
- MeSH Terms
- Animals, Genetically Modified
- Brain/blood supply
- Endothelial Cells/metabolism
- Endothelial Cells/physiology*
- Endothelial Cells/ultrastructure
- Lipoproteins, LDL/metabolism
- Meninges/blood supply*
- Meninges/growth & development
- Neovascularization, Physiologic/physiology*
- Signal Transduction/physiology
- Vascular Endothelial Growth Factors/biosynthesis
- Vascular Endothelial Growth Factors/physiology*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Zebrafish Proteins/physiology*
- 28459441 Full text @ Nat. Neurosci.
Bower, N.I., Koltowska, K., Pichol-Thievend, C., Virshup, I., Paterson, S., Lagendijk, A.K., Wang, W., Lindsey, B.W., Bent, S.J., Baek, S., Rondon-Galeano, M., Hurley, D.G., Mochizuki, N., Simons, C., Francois, M., Wells, C.A., Kaslin, J., Hogan, B.M. (2017) Mural lymphatic endothelial cells regulate meningeal angiogenesis in the zebrafish. Nature Neuroscience. 20(6):774-783.
Mural cells of the vertebrate brain maintain vascular integrity and function, play roles in stroke and are involved in maintenance of neural stem cells. However, the origins, diversity and roles of mural cells remain to be fully understood. Using transgenic zebrafish, we identified a population of isolated mural lymphatic endothelial cells surrounding meningeal blood vessels. These meningeal mural lymphatic endothelial cells (muLECs) express lymphatic endothelial cell markers and form by sprouting from blood vessels. In larvae, muLECs develop from a lymphatic endothelial loop in the midbrain into a dispersed, nonlumenized mural lineage. muLEC development requires normal signaling through the Vegfc-Vegfd-Ccbe1-Vegfr3 pathway. Mature muLECs produce vascular growth factors and accumulate low-density lipoproteins from the bloodstream. We find that muLECs are essential for normal meningeal vascularization. Together, these data identify an unexpected lymphatic lineage and developmental mechanism necessary for establishing normal meningeal blood vasculature.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes