Development and plasticity of meningeal lymphatic vessels

DOI PDF 3 Citations
  • Salli Antila
    Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland 1
  • Sinem Karaman
    Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland 1
  • Harri Nurmi
    Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland 1
  • Mikko Airavaara
    Program in Developmental Biology, Institute of Biotechnology, HiLIFE Unit, University of Helsinki, Helsinki, Finland 2
  • Merja H. Voutilainen
    Program in Developmental Biology, Institute of Biotechnology, HiLIFE Unit, University of Helsinki, Helsinki, Finland 2
  • Thomas Mathivet
    Institut National de la Santé et de la Recherche Médicale U970, Paris Cardiovascular Research Center, Paris, France 3
  • Dmitri Chilov
    Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland 1
  • Zhilin Li
    Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland 1
  • Tapani Koppinen
    Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland 1
  • Jun-Hee Park
    Department of Neurology, Yale University School of Medicine, New Haven, CT 4
  • Shentong Fang
    Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland 1
  • Aleksanteri Aspelund
    Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland 1
  • Mart Saarma
    Program in Developmental Biology, Institute of Biotechnology, HiLIFE Unit, University of Helsinki, Helsinki, Finland 2
  • Anne Eichmann
    Institut National de la Santé et de la Recherche Médicale U970, Paris Cardiovascular Research Center, Paris, France 3
  • Jean-Léon Thomas
    Department of Neurology, Yale University School of Medicine, New Haven, CT 4
  • Kari Alitalo
    Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland 1

Description

<jats:p>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.</jats:p>

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