Cyclooxygenase-1 derived prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) signaling in early development
Cha, Yong I.
Prostaglandin G/H synthases (PGHS), commonly referred to as cyclooxygenases (COX-1 and COX-2), catalyze a key step in the synthesis of biologically active prostaglandins (PGs), the conversion of arachidonic acid (AA) into prostaglandin H<sub>2</sub> (PGH<sub>2</sub>). PGs have important functions in a variety of physiologic and pathologic settings, including inflammation, cardiovascular homeostasis, reproduction, and carcinogenesis. However an evaluation of prostaglandin function in early mammalian development has been difficult due to the maternal contribution of prostaglandins from the uterus. The emergence of zebrafish as a model system has begun to provide some insights into the roles of this signaling cascade during vertebrate development. In zebrafish, COX-1 derived prostaglandins are required for two distinct stages of development, namely during gastrulation and segmentation. During gastrulation, PGE<sub>2</sub> signaling promotes cell motility, without altering the cell shape or directional migration of gastrulating mesodermal cells via the G-protein coupled prostaglandin E<sub>2</sub> receptor (EP4). During segmentation, COX-1 signaling is also required for posterior mesoderm development, including the formation of vascular tube structures, angiogenesis of intersomitic vessels, and pronephros morphogenesis. We propose that deciphering the role for prostaglandin signaling in zebrafish development could delineate mechanistic details underlying various disease processes that result from perturbation of this pathway and uncover novel potential therapeutic targets.