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Cerebral cavernous malformations arise from endothelial gain of MEKK3–KLF2/4 signalling

Author

Listed:
  • Zinan Zhou

    (University of Pennsylvania, 3400 Civic Center Blvd)

  • Alan T. Tang

    (University of Pennsylvania, 3400 Civic Center Blvd)

  • Weng-Yew Wong

    (Laboratory of Cardiovascular Signaling, Centenary Institute)

  • Sharika Bamezai

    (University of Pennsylvania, 3400 Civic Center Blvd)

  • Lauren M. Goddard

    (University of Pennsylvania, 3400 Civic Center Blvd)

  • Robert Shenkar

    (Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine and Biological Sciences)

  • Su Zhou

    (University of Pennsylvania, 3400 Civic Center Blvd)

  • Jisheng Yang

    (University of Pennsylvania, 3400 Civic Center Blvd)

  • Alexander C. Wright

    (University of Pennsylvania Medical Center)

  • Matthew Foley

    (Sydney Microscopy & Microanalysis, University of Sydney)

  • J. Simon C. Arthur

    (University of Dundee)

  • Kevin J. Whitehead

    (University of Utah)

  • Issam A. Awad

    (Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine and Biological Sciences)

  • Dean Y. Li

    (University of Utah
    The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital)

  • Xiangjian Zheng

    (Laboratory of Cardiovascular Signaling, Centenary Institute
    Faculty of Medicine, Sydney Medical School, University of Sydney)

  • Mark L. Kahn

    (University of Pennsylvania, 3400 Civic Center Blvd)

Abstract

Gain of MEKK3 signalling is shown to cause cerebral cavernous malformations (CCMs) via activation of the target genes Klf2 and Klf4; endothelial-specific loss of MEKK3, KLF2 or KLF4 prevents lesion formation and lethality in a mouse CCM model.

Suggested Citation

  • Zinan Zhou & Alan T. Tang & Weng-Yew Wong & Sharika Bamezai & Lauren M. Goddard & Robert Shenkar & Su Zhou & Jisheng Yang & Alexander C. Wright & Matthew Foley & J. Simon C. Arthur & Kevin J. Whitehea, 2016. "Cerebral cavernous malformations arise from endothelial gain of MEKK3–KLF2/4 signalling," Nature, Nature, vol. 532(7597), pages 122-126, April.
    • Handle: RePEc:nat:nature:v:532:y:2016:i:7597:d:10.1038_nature17178
    DOI: 10.1038/nature17178
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    Cited by:

    1. Andrew K. Ressler & Daniel A. Snellings & Romuald Girard & Carol J. Gallione & Rhonda Lightle & Andrew S. Allen & Issam A. Awad & Douglas A. Marchuk, 2023. "Single-nucleus DNA sequencing reveals hidden somatic loss-of-heterozygosity in Cerebral Cavernous Malformations," Nature Communications, Nature, vol. 14(1), pages 1-9, December.

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