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

Yong I. Cha, Seok Hyung Kim, Diane Sepich, F. Gregory Buchanan, Lilianna Solnica-Krezel, Raymond N. DuBois

Research output: Contribution to journalArticle

63 Scopus citations

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 E 2 (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.

Original languageEnglish
Pages (from-to)77-86
Number of pages10
JournalGenes and Development
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

Keywords

  • Cancer
  • Cell motility
  • Cyclooxygenase
  • Development
  • Prostaglandin
  • Zebrafish

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