PUBLICATION

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

Authors
Cha, Y.I., Kim, S.H., Sepich, D., Buchanan, F.G., Solnica-Krezel, L., and Dubois, R.N.
ID
ZDB-PUB-060113-2
Date
2006
Source
Genes & Development   20(1): 77-86 (Journal)
Registered Authors
Kim, Seok-Hyung, Sepich, Diane, Solnica-Krezel, Lilianna
Keywords
Cancer, cell motility, cyclooxygenase, development, prostaglandin, zebrafish
MeSH Terms
  • Animals
  • Cell Movement*
  • Cyclooxygenase 1/genetics
  • Cyclooxygenase 1/physiology*
  • Dinoprostone/metabolism
  • Dinoprostone/physiology*
  • Gastrula/physiology*
  • Intramolecular Oxidoreductases/metabolism
  • Phosphatidylinositol 3-Kinases/metabolism
  • Receptors, Prostaglandin E/genetics
  • Receptors, Prostaglandin E/metabolism
  • Receptors, Prostaglandin E/physiology*
  • Receptors, Prostaglandin E, EP4 Subtype
  • Signal Transduction
  • Zebrafish/embryology
  • Zebrafish/physiology*
(all 16)
PubMed
16391234 Full text @ Genes & Dev.
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) (PGE(2)) production by microsomal PGE(2) synthase (Ptges) is essential for gastrulation movements in zebrafish. Furthermore, PGE(2) signaling regulates morphogenetic movements of convergence and extension as well as epiboly through the G-protein-coupled PGE(2) 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 PGE(2) 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.
Genes / Markers
Marker Marker Type Name
bmp4GENEbone morphogenetic protein 4
gscGENEgoosecoid
pax2aGENEpaired box 2a
ptger2aGENEprostaglandin E receptor 2a (subtype EP2)
ptger4aGENEprostaglandin E receptor 4 (subtype EP4) a
ptgesGENEprostaglandin E synthase
ptgs1GENEprostaglandin-endoperoxide synthase 1
ptgs2aGENEprostaglandin-endoperoxide synthase 2a
six3bGENESIX homeobox 3b
tbxtaGENET-box transcription factor Ta
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Figures
Figure Gallery (6 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO1-ptger2astandard conditionsBud
WT + MO1-ptgesstandard conditionsBud
WT + MO1-ptgesstandard conditionsBud
WT + MO1-ptgesstandard conditionsBud
WT + MO1-ptgesstandard conditionsBud
WT + MO2-ptger4astandard conditionsShield
WT + MO2-ptger4astandard conditionsShield
WT + MO2-ptger4astandard conditions1-4 somites
WT + MO2-ptger4astandard conditionsBud
WT + MO2-ptger4astandard conditions1-4 somites
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Mutations / Transgenics
No data available
Human Disease / Model
No data available
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
No data available
Mapping
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Citation
Cha, Y.I., Kim, S.H., Sepich, D., Buchanan, F.G., Solnica-Krezel, L., and Dubois, R.N. (2006) Cyclooxygenase-1-derived PGE2 promotes cell motility via the G-protein-coupled EP4 receptor during vertebrate gastrulation. Genes & Development. 20(1):77-86.