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Genes & Dev. 20 (1): 77-86

Copyright © 2006 by Cold Spring Harbor Laboratory Press.


RESEARCH PAPER

Cyclooxygenase-1-derived PGE2 promotes cell motility via the G-protein-coupled EP4 receptor during vertebrate gastrulation

Yong I. Cha1, Seok-Hyung Kim2, Diane Sepich2, 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

Abstract: Gastrulation is a fundamental process during embryogenesis that shapes proper body architecture and establishes three germ layers through coordinated cellular actions of proliferation, fate specification, and movement. Although many molecular pathways involved in the specification of cell fate and polarity during vertebrate gastrulation have been identified, little is known of the signaling that imparts cell motility. Here we show that prostaglandin E2 (PGE2) production by microsomal PGE2 synthase (Ptges) is essential for gastrulation movements in zebrafish. Furthermore, PGE2 signaling regulates morphogenetic movements of convergence and extension as well as epiboly through the G-protein-coupled PGE2 receptor (EP4) via phosphatidylinositol 3-kinase (PI3K)/Akt. EP4 signaling is not required for proper cell shape or persistence of migration, but rather it promotes optimal cell migration speed during gastrulation. This work demonstrates a critical requirement of PGE2 signaling in promoting cell motility through the COX-1–Ptges–EP4 pathway, a previously unrecognized role for this biologically active lipid 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.

3 These authors contributed equally to this work.

4 Corresponding author.

E-MAIL raymond.dubois{at}vanderbilt.edu; FAX (615) 936-2697.


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