PUBLICATION

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

Authors
Cha, Y.I., Kim, S.H., Solnica-Krezel, L., and Dubois, R.N.
ID
ZDB-PUB-050607-18
Date
2005
Source
Developmental Biology   282(1): 274-283 (Journal)
Registered Authors
Kim, Seok-Hyung, Solnica-Krezel, Lilianna
Keywords
Cyclooxygenase; Prostaglandin; Prostaglandin E2 (PGE2); Zebrafish; Tubulogenesis; Vascular tube; Angiogenesis; Kidney; Nephric duct; Posterior mesoderm
MeSH Terms
  • Animals
  • Blood Vessels/drug effects
  • Blood Vessels/embryology*
  • Cyclooxygenase 1
  • Cyclooxygenase Inhibitors/pharmacology*
  • Dinoprostone/pharmacology
  • Gastrula/drug effects
  • Gastrula/physiology*
  • In Situ Hybridization
  • Mesoderm/metabolism
  • Microinjections
  • Oligonucleotides, Antisense/genetics
  • Prostaglandin-Endoperoxide Synthases/metabolism*
  • Signal Transduction/drug effects
  • Signal Transduction/physiology*
  • Zebrafish/embryology*
PubMed
15936346 Full text @ Dev. Biol.
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.
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