Cyclooxygenase-1 signaling is required for vascular tube formation during development

Yong I. Cha, Seok Hyung Kim, Lilianna Solnica-Krezel, Raymond N. DuBois

    Research output: Contribution to journalArticlepeer-review

    56 Scopus citations


    Prostaglandin endoperoxide synthases (PTGS), commonly referred to as cyclooxygenases (COX-1 and COX-2), catalyze the key step in the synthesis of biologically active prostaglandins (PGs), the conversion of arachidonic acid (AA) into prostaglandin H2 (PGH2). Although COX and prostaglandins have been implicated in a wide variety of physiologic processes, an evaluation of the role of prostaglandins in early mammalian development has been difficult due to the maternal contribution of prostaglandins from the uterus: COX null mouse embryos develop normally during embryogenesis. Here, we verify that inhibition of COX-1 results in zebrafish gastrulation arrest and shows that COX-1 expression becomes restricted to the posterior mesoderm during somitogenesis and to posterior mesoderm organs at pharyngula stage. Inhibition of COX-1 signaling after gastrulation results in defective vascular tube formation and shortened intersomitic vessels in the posterior body region. These defects are rescued completely by PGE2 treatment or, to a lesser extent, by PGF , but not by other prostaglandins, such as PGI2, TxB2, or PGD2. Functional knockdown of COX-1 using antisense morpholino oligonucleotide translation interference also results in posterior vessel defect in addition to enlarged posterior nephric duct, phenocopying the defects caused by inhibition of COX-1 activity. Together, we provide the first evidence that COX-1 signaling is required for development of posterior mesoderm organs, specifically in the vascular tube formation and posterior nephric duct development.

    Original languageEnglish (US)
    Pages (from-to)274-283
    Number of pages10
    JournalDevelopmental Biology
    Issue number1
    StatePublished - Jun 1 2005


    • Angiogenesis
    • Cyclooxygenase
    • Kidney
    • Nephric duct
    • Posterior mesoderm
    • Prostaglandin
    • Prostaglandin E (PGE)
    • Tubulogenesis
    • Vascular tube
    • Zebrafish

    ASJC Scopus subject areas

    • Molecular Biology
    • Developmental Biology
    • Cell Biology

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