Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development

The lymphatic system controls fluid homeostasis and the clearance of macromolecules from interstitial compartments. In mammals brain lymphatics were only recently discovered, with significant implications for physiology and disease. We examined zebrafish for the presence of brain lymphatics and foun...

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Main Authors: Max van Lessen, Shannon Shibata-Germanos, Andreas van Impel, Thomas A Hawkins, Jason Rihel, Stefan Schulte-Merker
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2017-05-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/25932
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author Max van Lessen
Shannon Shibata-Germanos
Andreas van Impel
Thomas A Hawkins
Jason Rihel
Stefan Schulte-Merker
author_facet Max van Lessen
Shannon Shibata-Germanos
Andreas van Impel
Thomas A Hawkins
Jason Rihel
Stefan Schulte-Merker
author_sort Max van Lessen
collection DOAJ
description The lymphatic system controls fluid homeostasis and the clearance of macromolecules from interstitial compartments. In mammals brain lymphatics were only recently discovered, with significant implications for physiology and disease. We examined zebrafish for the presence of brain lymphatics and found loosely connected endothelial cells with lymphatic molecular signature covering parts of the brain without forming endothelial tubular structures. These brain lymphatic endothelial cells (BLECs) derive from venous endothelium, are distinct from macrophages, and are sensitive to loss of Vegfc. BLECs endocytose macromolecules in a selective manner, which can be blocked by injection of mannose receptor ligands. This first report on brain lymphatic endothelial cells in a vertebrate embryo identifies cells with unique features, including the uptake of macromolecules at a single cell level. Future studies will address whether this represents an uptake mechanism that is conserved in mammals and how these cells affect functions of the embryonic and adult brain.
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spelling doaj.art-c4e7fc95512841e39cabefef9b191d7b2022-12-22T03:53:02ZengeLife Sciences Publications LtdeLife2050-084X2017-05-01610.7554/eLife.25932Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic developmentMax van Lessen0Shannon Shibata-Germanos1https://orcid.org/0000-0002-4250-7497Andreas van Impel2https://orcid.org/0000-0002-4737-3547Thomas A Hawkins3Jason Rihel4https://orcid.org/0000-0003-4067-2066Stefan Schulte-Merker5https://orcid.org/0000-0003-3617-8807Institute of Cardiovascular Organogenesis and Regeneration, WWU Münster, Münster, Germany; Faculty of Medicine, WWU Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence, WWU Münster, Münster, GermanyDepartment of Cell and Developmental Biology, University College London, London, United KingdomInstitute of Cardiovascular Organogenesis and Regeneration, WWU Münster, Münster, Germany; Faculty of Medicine, WWU Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence, WWU Münster, Münster, GermanyDepartment of Cell and Developmental Biology, University College London, London, United KingdomDepartment of Cell and Developmental Biology, University College London, London, United KingdomInstitute of Cardiovascular Organogenesis and Regeneration, WWU Münster, Münster, Germany; Faculty of Medicine, WWU Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence, WWU Münster, Münster, GermanyThe lymphatic system controls fluid homeostasis and the clearance of macromolecules from interstitial compartments. In mammals brain lymphatics were only recently discovered, with significant implications for physiology and disease. We examined zebrafish for the presence of brain lymphatics and found loosely connected endothelial cells with lymphatic molecular signature covering parts of the brain without forming endothelial tubular structures. These brain lymphatic endothelial cells (BLECs) derive from venous endothelium, are distinct from macrophages, and are sensitive to loss of Vegfc. BLECs endocytose macromolecules in a selective manner, which can be blocked by injection of mannose receptor ligands. This first report on brain lymphatic endothelial cells in a vertebrate embryo identifies cells with unique features, including the uptake of macromolecules at a single cell level. Future studies will address whether this represents an uptake mechanism that is conserved in mammals and how these cells affect functions of the embryonic and adult brain.https://elifesciences.org/articles/25932lymphaticsendothelial cellbrain
spellingShingle Max van Lessen
Shannon Shibata-Germanos
Andreas van Impel
Thomas A Hawkins
Jason Rihel
Stefan Schulte-Merker
Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development
eLife
lymphatics
endothelial cell
brain
title Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development
title_full Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development
title_fullStr Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development
title_full_unstemmed Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development
title_short Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development
title_sort intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development
topic lymphatics
endothelial cell
brain
url https://elifesciences.org/articles/25932
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AT shannonshibatagermanos intracellularuptakeofmacromoleculesbybrainlymphaticendothelialcellsduringzebrafishembryonicdevelopment
AT andreasvanimpel intracellularuptakeofmacromoleculesbybrainlymphaticendothelialcellsduringzebrafishembryonicdevelopment
AT thomasahawkins intracellularuptakeofmacromoleculesbybrainlymphaticendothelialcellsduringzebrafishembryonicdevelopment
AT jasonrihel intracellularuptakeofmacromoleculesbybrainlymphaticendothelialcellsduringzebrafishembryonicdevelopment
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