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J Exp Med. 2017 Dec 4;214(12):3645-3667. doi: 10.1084/jem.20170391. Epub 2017 Nov 15.

Development and plasticity of meningeal lymphatic vessels.

Author information

1
Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
2
Program in Developmental Biology, Institute of Biotechnology, HiLIFE Unit, University of Helsinki, Helsinki, Finland.
3
Institut National de la Santé et de la Recherche Médicale U970, Paris Cardiovascular Research Center, Paris, France.
4
Department of Neurology, Yale University School of Medicine, New Haven, CT.
5
Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
6
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT.
7
Sorbonne Universités, UPMC Université Paris 06, Institut National de la Santé et de la Recherche Médicale U1127, Centre National de la Recherche Scientifique, AP-HP, Institut du Cerveau et de la Moelle Epinière, Hôpital Pitié-Salpêtrière, Paris, France.
8
Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland kari.alitalo@helsinki.fi.

Abstract

The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement in neuropathological processes, yet little is known about their development or maintenance. We show here that meningeal LVs develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system (CNS). VEGF-C, expressed mainly in vascular smooth muscle cells, and VEGFR3 in lymphatic endothelial cells were essential for their development, whereas VEGF-D deletion had no effect. Surprisingly, in adult mice, the LVs showed regression after VEGF-C or VEGFR3 deletion, administration of the tyrosine kinase inhibitor sunitinib, or expression of VEGF-C/D trap, which also compromised the lymphatic drainage function. Conversely, an excess of VEGF-C induced meningeal lymphangiogenesis. The plasticity and regenerative potential of meningeal LVs should allow manipulation of cerebrospinal fluid drainage and neuropathological processes in the CNS.

Comment in

PMID:
29141865
PMCID:
PMC5716035
DOI:
10.1084/jem.20170391
[Indexed for MEDLINE]
Free PMC Article

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