title: Cyclooxygenase-1 signaling is required for vascular tube formation during development.
abstract: 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 PGE(2) treatment or, to a lesser extent, by PGF(2alpha), but not by other prostaglandins, such as PGI(2), TxB(2), or PGD(2). 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.
authors.affiliation: Department of Medicine, Cell and Developmental Biology and Cancer Biology, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University, 694 Preston Research Building, 2300 Pierce Ave, Nashville, TN 37232, USA.
authors.forename: Yong I
authors.initials: YI
authors.lastname: Cha
authors.forename: Seok-Hyung
authors.initials: SH
authors.lastname: Kim
authors.forename: Lilianna
authors.initials: L
authors.lastname: Solnica-Krezel
authors.forename: Raymond N
authors.initials: RN
authors.lastname: Dubois
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000196:embryology*; D051545:Cyclooxygenase 1; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D005775:Gastrula / Q000187:drug effects / Q000502:physiology*; D017403:In Situ Hybridization; D008648:Mesoderm / Q000378:metabolism; D008845:Microinjections; D016376:Oligonucleotides, Antisense / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D016376:Oligonucleotides, Antisense; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone