Mural lymphatic endothelial cells regulate meningeal angiogenesis in the zebrafish

Neil I Bower, Katarzyna Koltowska, Cathy Pichol-Thievend, Isaac Virshup, Scott Paterson, Anne K. Lagendijk, Weili Wang, Benjamin W. Lindsey, Stephen J. Bent, Sungmin Baek, Maria Rondon-Galeano, Daniel G. Hurley, Naoki Mochizuki, Cas Simons, Mathias Francois, Christine A Wells, Jan Kaslin, Benjamin M. Hogan

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)774-783
Number of pages10
JournalNature Neuroscience
Volume20
Issue number6
DOIs
Publication statusPublished - 1 Jun 2017

Keywords

  • blood-brain barrier
  • cell lineage

Cite this

Bower, N. I., Koltowska, K., Pichol-Thievend, C., Virshup, I., Paterson, S., Lagendijk, A. K., ... Hogan, B. M. (2017). Mural lymphatic endothelial cells regulate meningeal angiogenesis in the zebrafish. Nature Neuroscience, 20(6), 774-783. https://doi.org/10.1038/nn.4558
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. / Mural lymphatic endothelial cells regulate meningeal angiogenesis in the zebrafish. In: Nature Neuroscience. 2017 ; Vol. 20, No. 6. pp. 774-783.
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Bower, NI, Koltowska, K, Pichol-Thievend, C, Virshup, I, Paterson, S, Lagendijk, AK, Wang, W, Lindsey, BW, Bent, SJ, Baek, S, Rondon-Galeano, M, Hurley, DG, Mochizuki, N, Simons, C, Francois, M, Wells, CA, Kaslin, J & Hogan, BM 2017, 'Mural lymphatic endothelial cells regulate meningeal angiogenesis in the zebrafish', Nature Neuroscience, vol. 20, no. 6, pp. 774-783. https://doi.org/10.1038/nn.4558

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; Hogan, Benjamin M.

In: Nature Neuroscience, Vol. 20, No. 6, 01.06.2017, p. 774-783.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Mural lymphatic endothelial cells regulate meningeal angiogenesis in the zebrafish

AU - Bower, Neil I

AU - Koltowska, Katarzyna

AU - Pichol-Thievend, Cathy

AU - Virshup, Isaac

AU - Paterson, Scott

AU - Lagendijk, Anne K.

AU - Wang, Weili

AU - Lindsey, Benjamin W.

AU - Bent, Stephen J.

AU - Baek, Sungmin

AU - Rondon-Galeano, Maria

AU - Hurley, Daniel G.

AU - Mochizuki, Naoki

AU - Simons, Cas

AU - Francois, Mathias

AU - Wells, Christine A

AU - Kaslin, Jan

AU - Hogan, Benjamin M.

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Y1 - 2017/6/1

N2 - 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.

AB - 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.

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KW - cell lineage

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U2 - 10.1038/nn.4558

DO - 10.1038/nn.4558

M3 - Article

VL - 20

SP - 774

EP - 783

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

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ER -

Bower NI, Koltowska K, Pichol-Thievend C, Virshup I, Paterson S, Lagendijk AK et al. Mural lymphatic endothelial cells regulate meningeal angiogenesis in the zebrafish. Nature Neuroscience. 2017 Jun 1;20(6):774-783. https://doi.org/10.1038/nn.4558