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Dev Cell. 2019 Nov 4;51(3):374-386.e5. doi: 10.1016/j.devcel.2019.08.019. Epub 2019 Sep 26.

Valves Are a Conserved Feature of the Zebrafish Lymphatic System.

Author information

1
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
2
Technical Support Center for Life Science Research, Iwate Medical University, Shiwa, Iwate 028-3694, Japan.
3
Department of Medical Education, Iwate Medical University, Shiwa, Iwate 028-3694, Japan.
4
Department of Molecular Pathophysiology, Institute of Advanced Medical Sciences, Nippon Medical School, 1-396 Kosugi-machi, Nakahara-ku, Kawasaki, Kanagawa 211-8533, Japan.
5
Department of Cell Biology and AMED-CREST, National Cerebral and Cardiovascular Center, Research Institute, Suita, Osaka 565-8565, Japan.
6
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Ikeda, Osaka 563-8577, Japan.
7
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: nathan.lawson@umassmed.edu.

Abstract

The lymphatic system comprises blind-ended tubes that collect interstitial fluid and return it to the circulatory system. In mammals, unidirectional lymphatic flow is driven by muscle contraction working in conjunction with valves. Accordingly, defective lymphatic valve morphogenesis results in backflow leading to edema. In fish species, studies dating to the 18th century failed to identify lymphatic valves, a precedent that currently persists, raising the question of whether the zebrafish could be used to study the development of these structures. Here, we provide functional and morphological evidence of valves in the zebrafish lymphatic system. Electron microscopy revealed valve ultrastructure similar to mammals, while live imaging using transgenic lines identified the developmental origins of lymphatic valve progenitors. Zebrafish embryos bearing mutations in genes required for mammalian valve morphogenesis show defective lymphatic valve formation and edema. Together, our observations provide a foundation from which to further investigate lymphatic valve formation in zebrafish.

KEYWORDS:

lymphatic; lymphatic development; lymphatic valve; zebrafish

PMID:
31564611
PMCID:
PMC6832890
[Available on 2020-11-04]
DOI:
10.1016/j.devcel.2019.08.019

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