TY - JOUR
T1 - Cyclooxygenase-1 signaling is required for vascular tube formation during development
AU - Cha, Yong I.
AU - Kim, Seok Hyung
AU - Solnica-Krezel, Lilianna
AU - DuBois, Raymond N.
N1 - Funding Information:
We thank T. Grosser and G. Fitzgerald for full-length zebrafish COX-1 and COX-2 constructs; SK. Dey and J. Jessen for his invaluable assistance during the course of experiments; J. Morrow for prostaglandin measurements. This work is supported in part from the United States Public Health Services Grants RO-DK-62112 and P0-CA-77839. RND is the Hortense B. Ingram Professor of Molecular Oncology and the recipient of an NIH MERIT award (R37-DK47297). This research has been supported in part by a zebrafish initiative funded by the Vanderbilt University Academic Venture Capital Fund. We also thank the T.J. Martell Foundation and the National Colorectal Cancer Research.
PY - 2005/6/1
Y1 - 2005/6/1
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Cyclooxygenase
KW - Kidney
KW - Nephric duct
KW - Posterior mesoderm
KW - Prostaglandin
KW - Prostaglandin E (PGE)
KW - Tubulogenesis
KW - Vascular tube
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=20344364611&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2005.03.014
DO - 10.1016/j.ydbio.2005.03.014
M3 - Article
C2 - 15936346
AN - SCOPUS:20344364611
SN - 0012-1606
VL - 282
SP - 274
EP - 283
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -