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

54 Scopus citations

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 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
Pages (from-to)274-283
Number of pages10
JournalDevelopmental Biology
Volume282
Issue number1
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

Keywords

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

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