Mural lymphatic endothelial cells regulate meningeal angiogenesis in the zebrafish

Bower, Neil I., Koltowska, Katarzyna, Pichol-Thievend, Cathy, Virshup, Isaac, Paterson, Scott, Lagendijk, Anne K., Wang, Weili, Lindsey, Benjamin W., Bent, Stephen J., Baek, Sungmin, Rondon-Galeano, Maria, Hurley, Daniel G., Mochizuki, Naoki, Simons, Cas, Francois, Mathias, Wells, Christine A., Kaslin, Jan and Hogan, Benjamin M. (2017) Mural lymphatic endothelial cells regulate meningeal angiogenesis in the zebrafish. Nature Neuroscience, 20 6: 774-783. doi:10.1038/nn.4558

Author Bower, Neil I.
Koltowska, Katarzyna
Pichol-Thievend, Cathy
Virshup, Isaac
Paterson, Scott
Lagendijk, Anne K.
Wang, Weili
Lindsey, Benjamin W.
Bent, Stephen J.
Baek, Sungmin
Rondon-Galeano, Maria
Hurley, Daniel G.
Mochizuki, Naoki
Simons, Cas
Francois, Mathias
Wells, Christine A.
Kaslin, Jan
Hogan, Benjamin M.
Title Mural lymphatic endothelial cells regulate meningeal angiogenesis in the zebrafish
Journal name Nature Neuroscience   Check publisher's open access policy
ISSN 1546-1726
Publication date 2017-05-01
Sub-type Article (original research)
DOI 10.1038/nn.4558
Open Access Status Not yet assessed
Volume 20
Issue 6
Start page 774
End page 783
Total pages 11
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Language eng
Subject 2800 Neuroscience
Abstract 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.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1083811
Institutional Status UQ

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