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Cyclooxygenase-1-derived PGE2 promotes cell motility via the G-protein-coupled EP4 receptor during vertebrate gastrulation
Yong I. Cha1,
F. Gregory Buchanan1,
Lilianna Solnica-Krezel2,3, and
Raymond N. DuBois1,3,4
1 Department of Medicine and Cancer Biology, Cell and Developmental Biology, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, 37232-2279, USA; 2 Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, USA
Gastrulation is a fundamental process during embryogenesis thatshapes proper body architecture and establishes three germ layersthrough coordinated cellular actions of proliferation, fatespecification, and movement. Although many molecular pathwaysinvolved in the specification of cell fate and polarity duringvertebrate gastrulation have been identified, little is knownof the signaling that imparts cell motility. Here we show thatprostaglandin E2 (PGE2) production by microsomal PGE2 synthase(Ptges) is essential for gastrulation movements in zebrafish.Furthermore, PGE2 signaling regulates morphogenetic movementsof convergence and extension as well as epiboly through theG-protein-coupled PGE2 receptor (EP4) via phosphatidylinositol3-kinase (PI3K)/Akt. EP4 signaling is not required for propercell shape or persistence of migration, but rather it promotesoptimal cell migration speed during gastrulation. This workdemonstrates a critical requirement of PGE2 signaling in promotingcell motility through the COX-1PtgesEP4 pathway,a previously unrecognized role for this biologically activelipid in early animal development.
Key Words: Cancer cell motility cyclooxygenase development prostaglandin zebrafish
Received for publication September 13, 2005.
Accepted for publication November 14, 2005.
Supplemental material is available at http://www.genesdev.org.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1374506.