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Cytoglobin regulates NO-dependent cilia motility and organ laterality during development

Author

Listed:
  • Elizabeth R. Rochon

    (University of Maryland School of Medicine)

  • Jianmin Xue

    (University of Pittsburgh School of Medicine)

  • Manush Sayd Mohammed

    (University of Pittsburgh School of Medicine)

  • Caroline Smith

    (University of Pittsburgh School of Medicine)

  • Anders Hay-Schmidt

    (University of Copenhagen)

  • Anthony W. DeMartino

    (University of Maryland School of Medicine)

  • Adam Clark

    (University of Maryland School of Medicine)

  • Qinzi Xu

    (University of Maryland School of Medicine)

  • Cecilia W. Lo

    (University of Pittsburgh School of Medicine)

  • Michael Tsang

    (University of Pittsburgh School of Medicine)

  • Jesus Tejero

    (University of Pittsburgh School of Medicine
    University of Pittsburgh School of Medicine
    University of Pittsburgh Swanson School of Engineering
    University of Pittsburgh)

  • Mark T. Gladwin

    (University of Maryland School of Medicine)

  • Paola Corti

    (University of Maryland School of Medicine)

Abstract

Cytoglobin is a heme protein with unresolved physiological function. Genetic deletion of zebrafish cytoglobin (cygb2) causes developmental defects in left-right cardiac determination, which in humans is associated with defects in ciliary function and low airway epithelial nitric oxide production. Here we show that Cygb2 co-localizes with cilia and with the nitric oxide synthase Nos2b in the zebrafish Kupffer’s vesicle, and that cilia structure and function are disrupted in cygb2 mutants. Abnormal ciliary function and organ laterality defects are phenocopied by depletion of nos2b and of gucy1a, the soluble guanylate cyclase homolog in fish. The defects are rescued by exposing cygb2 mutant embryos to a nitric oxide donor or a soluble guanylate cyclase stimulator, or with over-expression of nos2b. Cytoglobin knockout mice also show impaired airway epithelial cilia structure and reduced nitric oxide levels. Altogether, our data suggest that cytoglobin is a positive regulator of a signaling axis composed of nitric oxide synthase–soluble guanylate cyclase–cyclic GMP that is necessary for normal cilia motility and left-right patterning.

Suggested Citation

  • Elizabeth R. Rochon & Jianmin Xue & Manush Sayd Mohammed & Caroline Smith & Anders Hay-Schmidt & Anthony W. DeMartino & Adam Clark & Qinzi Xu & Cecilia W. Lo & Michael Tsang & Jesus Tejero & Mark T. G, 2023. "Cytoglobin regulates NO-dependent cilia motility and organ laterality during development," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43544-0
    DOI: 10.1038/s41467-023-43544-0
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    References listed on IDEAS

    as
    1. Xiaoping Liu & Mohamed A. El-Mahdy & James Boslett & Saradhadevi Varadharaj & Craig Hemann & Tamer M. Abdelghany & Raed S. Ismail & Sean C. Little & Danlei Zhou & Le Thi Thanh Thuy & Norifumi Kawada &, 2017. "Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
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