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 2α, 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 language | English (US) |
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Pages (from-to) | 274-283 |
Number of pages | 10 |
Journal | Developmental Biology |
Volume | 282 |
Issue number | 1 |
DOIs | |
State | Published - Jun 1 2005 |
Externally published | Yes |
Keywords
- 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