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An NKX-COUP-TFII morphogenetic code directs mucosal endothelial addressin expression

Author

Listed:
  • Thanh Theresa Dinh

    (Stanford University School of Medicine
    Palo Alto Veterans Institute for Research)

  • Menglan Xiang

    (Stanford University School of Medicine
    Palo Alto Veterans Institute for Research)

  • Anusha Rajaraman

    (Stanford University School of Medicine
    Palo Alto Veterans Institute for Research
    Vrije Universiteit Medical Center)

  • Yongzhi Wang

    (Stanford University School of Medicine
    Lund University)

  • Nicole Salazar

    (Stanford University School of Medicine)

  • Yu Zhu

    (Stanford University School of Medicine)

  • Walter Roper

    (Columbia University Vagelos College of Physicians and Surgeons)

  • Siyeon Rhee

    (Stanford University)

  • Kevin Brulois

    (Stanford University School of Medicine
    Palo Alto Veterans Institute for Research)

  • Ed O’Hara

    (Palo Alto Veterans Institute for Research)

  • Helena Kiefel

    (Stanford University School of Medicine)

  • Truc M. Dinh

    (Palo Alto Veterans Institute for Research)

  • Yuhan Bi

    (Stanford University School of Medicine
    Palo Alto Veterans Institute for Research)

  • Dalila Gonzalez

    (University of California, San Diego)

  • Evan P. Bao

    (Palo Alto Veterans Institute for Research)

  • Kristy Red-Horse

    (Stanford University
    Stanford University School of Medicine
    Howard Hughes Medical Institute)

  • Peter Balogh

    (University of Pécs Medical School
    Lymphoid Organogenesis Research Team, Szentágothai Research Center)

  • Fanni Gábris

    (University of Pécs Medical School
    Lymphoid Organogenesis Research Team, Szentágothai Research Center)

  • Balázs Gaszner

    (University of Pécs Medical School)

  • Gergely Berta

    (University of Pécs Medical School)

  • Junliang Pan

    (Palo Alto Veterans Institute for Research
    The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System)

  • Eugene C. Butcher

    (Stanford University School of Medicine
    Palo Alto Veterans Institute for Research
    The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System)

Abstract

Immunoglobulin family and carbohydrate vascular addressins encoded by Madcam1 and St6gal1 control lymphocyte homing into intestinal tissues, regulating immunity and inflammation. The addressins are developmentally programmed to decorate endothelial cells lining gut post-capillary and high endothelial venules (HEV), providing a prototypical example of organ- and segment-specific endothelial specialization. We identify conserved NKX-COUP-TFII composite elements (NCCE) in regulatory regions of Madcam1 and St6gal1 that bind intestinal homeodomain protein NKX2-3 cooperatively with venous nuclear receptor COUP-TFII to activate transcription. The Madcam1 element also integrates repressive signals from arterial/capillary Notch effectors. Pan-endothelial COUP-TFII overexpression induces ectopic addressin expression in NKX2-3+ capillaries, while NKX2-3 deficiency abrogates expression by HEV. Phylogenetically conserved NCCE are enriched in genes involved in neuron migration and morphogenesis of the heart, kidney, pancreas and other organs. Our results define an NKX-COUP-TFII morphogenetic code that targets expression of mucosal vascular addressins.

Suggested Citation

  • Thanh Theresa Dinh & Menglan Xiang & Anusha Rajaraman & Yongzhi Wang & Nicole Salazar & Yu Zhu & Walter Roper & Siyeon Rhee & Kevin Brulois & Ed O’Hara & Helena Kiefel & Truc M. Dinh & Yuhan Bi & Dali, 2022. "An NKX-COUP-TFII morphogenetic code directs mucosal endothelial addressin expression," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34991-2
    DOI: 10.1038/s41467-022-34991-2
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    References listed on IDEAS

    as
    1. Li-Ru You & Fu-Jung Lin & Christopher T. Lee & Francesco J. DeMayo & Ming-Jer Tsai & Sophia Y. Tsai, 2005. "Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity," Nature, Nature, vol. 435(7038), pages 98-104, May.
    2. Kevin Brulois & Anusha Rajaraman & Agata Szade & Sofia Nordling & Ania Bogoslowski & Denis Dermadi & Milladur Rahman & Helena Kiefel & Edward O’Hara & Jasper J. Koning & Hiroto Kawashima & Bin Zhou & , 2020. "A molecular map of murine lymph node blood vascular endothelium at single cell resolution," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    3. San-Pin Wu & Chung-Yang Kao & Leiming Wang & Chad J. Creighton & Jin Yang & Taraka R. Donti & Romain Harmancey & Hernan G. Vasquez & Brett H. Graham & Hugo J. Bellen & Heinrich Taegtmeyer & Ching-Pin , 2015. "Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
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