Document Detail


Cyclooxygenase-1-derived PGE2 promotes cell motility via the G-protein-coupled EP4 receptor during vertebrate gastrulation.
MedLine Citation:
PMID:  16391234     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yong I Cha; Seok-Hyung Kim; Diane Sepich; F Gregory Buchanan; Lilianna Solnica-Krezel; Raymond N DuBois
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes & development     Volume:  20     ISSN:  0890-9369     ISO Abbreviation:  Genes Dev.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-01-04     Completed Date:  2006-03-14     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  77-86     Citation Subset:  IM    
Affiliation:
Department of Medicine and Cancer Biology, Cell and Developmental Biology, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232-2279, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Movement*
Cyclooxygenase 1 / genetics,  physiology*
Dinoprostone / metabolism,  physiology*
Gastrula / physiology*
Intramolecular Oxidoreductases / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Receptors, Prostaglandin E / genetics,  metabolism,  physiology*
Receptors, Prostaglandin E, EP4 Subtype
Signal Transduction
Zebrafish / embryology,  physiology*
Grant Support
ID/Acronym/Agency:
P0-CA-77839/CA/NCI NIH HHS; R0-DK-62112/DK/NIDDK NIH HHS; R01GM55101/GM/NIGMS NIH HHS; R37-DK47297/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Prostaglandin E; 0/Receptors, Prostaglandin E, EP4 Subtype; 363-24-6/Dinoprostone; EC 1.14.99.1/Cyclooxygenase 1; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.99.3/prostaglandin-E synthase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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